Biomedical subjects

H Arai

Publications and source records attributed to H Arai.

At least 235 records · Page 13Linked to original sources

PubMed1999

Iatrogenic cataract after laser-assisted in situ keratomileusis.

PURPOSE: To report a case of corneal opacity and iatrogenic cataract after laser-assisted in situ keratomileusis. METHOD: Case report. A 44-year-old man was initially seen with a traumatic cataract, corneal stromal opacity, and defect of the endothelium in the right eye after laser-assisted in situ keratomileusis performed by a plastic surgeon who had no ophthalmologic training. RESULTS: It was speculated that repeated ablations resulted in corneal perforation. We immediately performed phacoemulisification to remove the cataract and to prevent phacolytic glaucoma. However, visual acuity remained 20/200 because of the corneal stromal opacity, and penetrating keratoplasty was performed 2 months later, which improved best-corrected visual acuity to 20/30. CONCLUSIONS: This case demonstrated that laser-assisted in situ keratomileusis can cause devastating damage to the eye.

Adult↗

PubMed1999

Lysophosphatidylcholine activates mitogen-activated protein kinases by a tyrosine kinase-dependent pathway in bovine aortic endothelial cells.

Lysophosphatidylcholine (lyso-PC) is a major component of an atherogenic lipoprotein. In this study, to investigate the involvement of mitogen-activated protein kinases in the signaling pathway by lyso-PC in endothelial cells, we measured the activity of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in bovine aortic endothelial cells. Lyso-PC activated ERK and JNK in a dose-dependent manner. However, the time courses of activation of these kinases were different. ERK and JNK activation by lyso-PC was inhibited by a tyrosine kinase inhibitor, herbimycin A, but not by a protein kinase C (PKC) specific inhibitor. We conclude, therefore, that lyso-PC-mediated ERK and JNK activation is caused by a tyrosine kinase-dependent mechanism, but not conventional types of PKC-dependent mechanisms.

Animals↗

PubMed1999

Immunohistochemical study on transforming growth factor-beta1 expression in liver fibrosis of Down's syndrome with transient abnormal myelopoiesis.

A case of Down's syndrome associated with liver fibrosis is reported. The fibrosis was diffusely distributed along sinusoids, and an excess of megakaryocytes was also found in the liver. To determine the mechanism of liver fibrosis in Down's syndrome, we immunohistochemically stained the liver with markers of myofibroblast-like cells, antialpha smooth muscle actin antibodies and antidesmin antibodies. The myofibroblast-like cells were found along sinusoids, suggesting that liver fibrosis in Down's syndrome is caused by the myofibroblast-like cells derived from Ito cells/lipocytes. The expression of transforming growth factor (TGF)-betal, which is an important mediator of the activation of lipocytes, was immunohistochemically examined. The accumulation of TGF-betal was observed in cells in the sinusoidal spaces, which involve the intracellular expression of megakaryocytes. Together, these findings suggest that megakaryocyte-derived TGF-betal is one of the likely candidates in the lipocyte activation of liver fibrogenesis in Down's syndrome.

Actins↗

PubMed1999

Oxidized LDL and expression of monocyte adhesion molecules.

Accumulation of substantial numbers of monocyte/macrophages, as well as activated T lymphocytes, in focal areas of arterial intima appears to be a hallmark of atherogenesis. Our report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherogenic lipoproteins, such as oxidized LDL and remnants lipoproteins in diabetic and type III hyperlipidemic patients, can upregulate adhesion molecules for monocytes and T lymphocytes, and growth factors, such as heparin-binding epidermal growth factor-like growth factor and PDGF-A and B chains. Recently we identified the novel receptor for oxidized LDL, named Lox-1. Therefore in this paper we summarize the importance of the interaction between oxidized LDL and its receptor, LOX-1 in terms of early stage of atherogenesis.

Animals↗

PubMed1999

Measurement of GABAergic parameters in the prefrontal cortex in schizophrenia: focus on GABA content, GABA(A) receptor alpha-1 subunit messenger RNA and human GABA transporter-1 (HGAT-1) messenger RNA expression.

The hypothesis that the pathophysiology of schizophrenia may be associated with a dysfunction in GABA transmission in the human prefrontal cortex was investigated. Human post mortem brain tissue from 10 control cases and six cases of schizophrenia were processed for amino acid analysis and for radioactive in situ hybridization. Laminae III and V of three prefrontal cortical areas were examined in detail, namely Brodmann areas 9, 10 and 11. Of these three areas significant changes in GABAergic markers were found only in areas 9 and 10. Of note, a significant decrease in the tissue content of GABA was observed and this was accompanied by a marked increase in the cellular expression of the GABA(A) receptor alpha-1 subunit messenger RNA and a marked decrease in the expression of human GABA transporter-1, the messenger RNA encoding the neuronal GABA transporter protein. The amino acid analysis data provided in this study coupled with the detailed cellular study of several GABAergic markers in the human prefrontal cortex provide direct evidence in support of a disturbance in GABA transmission in the prefrontal cortex, which may be loosely termed "hypofrontality".

Aged↗

PubMed1999

Asn-linked sugar chain structures of recombinant human thrombopoietin produced in Chinese hamster ovary cells.

Human thrombopoietin (TPO) that regulates the numbers of megakaryocytes and platelets is a heavily N- and O-glycosylated glycoprotein hormone with partial homology to human erythropoietin (EPO). We prepared recombinant human TPO produced in Chinese hamster ovary (CHO) cells and analyzed the sugar chain structures quantitatively using 2-aminobenzamide labeling, sequential glycosidase digestion and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS). We found bi-, tri- and tetraantennary complex-type sugar chains with one or two N-acetyllactosamine repeats, which are common to recombinant human EPO produced in CHO cells. On the other hand, there were triantennary sugar chains with one or two N-acetyllactosamine repeats that were specific to the recombinant human TPO, and their distributions of branch structures were also different. These results suggested that proximal protein structure should determine the branch structure of Asn-linked sugar chains in addition to the glycosyltransferases subset.

Animals↗

PubMed1999

Adaptation of Comamonas testosteroni TA441 to utilization of phenol by spontaneous mutation of the gene for a trans-acting factor.

Comamonas testosteroni TA441 adapts to utilization of phenol upon incubation with phenol as the major carbon source. Strain TA441 has a cluster of genes (aphKLMNOPQB) encoding the catabolic enzymes phenol hydroxylase and catechol 2,3-dioxygenase, and a divergently transcribed regulatory gene (aphR), but these genes are silent until adaptation occurs. We found another regulatory gene (aphS) downstream of aphR. AphS belongs to the GntR family of transcriptional regulators. All adapted strains were found to have mutations in the aphS gene or in the aphR-aphS intervening region. The adapted strains expressed phenol hydroxylase and catechol 2, 3-dioxygenase activity in the presence of phenol. The transcriptional activity of both the aphK and the aphR promoters was elevated in the adapted strains. A strain whose aphS gene was artificially disrupted was found to be able to grow using phenol, and the cells showed high levels of the above-mentioned transcriptional and enzymatic activities, indicating that adaptation was caused only by the mutation in the aphS gene. Gel retardation analysis revealed that AphS bound to two specific sites in the promoter region between aphK and aphR. These results indicate that the active aphS gene product acts as a trans-acting factor and represses transcription of the aph genes in strain TA441.

Adaptation, Physiological↗

PubMed1999

Analysis of lissencephaly-causing LIS1 mutations.

Mutations in the LIS1 gene may result in severe abnormalities of brain cortical layering known as lissencephaly. Most lissencephaly-causing LIS1 mutations are deletions that encompass the entire gene, therefore the mechanism of the disease is regarded as haploinsufficiency. So far, 13 different intragenic mutations have been reported: one point mutation, H149R; deletion of exon 9, which results in deleted acids Delta301-334; deletion of exon 4, which results in deleted amino acids Delta40-64; 10 mutations resulting in truncated proteins and one predicted to result in extra amino acids. We studied the consequences of the point mutation, deletion mutation and one of the reported truncations. In order to study LIS1 structure function, we introduced an additional point mutation and other truncations in different regions of the protein. The consequences of these mutations to protein folding were studied by gel filtration, sucrose density gradient centrifugation and measuring resistance to trypsin cleavage. On the basis of our results, we suggest that all truncation mutations and lissencephaly-causing point mutations or internal deletion result in a reduction in the amount of correctly folded LIS1 protein.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1999

Recent advances in dementia research in Japan: Alzheimer-type dementia.

In a previous article, recent reports by Japanese researchers on non-Alzheimer-type degenerative dementias were reviewed. In the present article, recent Japanese reports on Alzheimer-type dementia (ATD) are reviewed. Alzheimer-type dementia has received great attention and has been studied from various viewpoints in Japan as well as in Europe and the Americas. In Japan, although it was believed that vascular dementia was the most frequent dementia in the elderly, ATD has recently been shown to be the most predominant type of dementia. Such a great number of papers on ATD have been reported in Japan that mainly the clinical, neuropathological, biochemical and molecular biological research papers alone are reviewed here.

Adult↗

PubMed1999

Epworth Sleepiness Scale and sleep studies in patients with obstructive sleep apnea syndrome.

Excessive daytime sleepiness (EDS) is the major symptom of patients with obstructive sleep apnea syndrome (OSAS). In this study, we examined the relationship between subjective EDS scored with the Epworth Sleepiness Scale (ESS), objective EDS measured with the multiple sleep latency test (MSLT) and sleep variables evaluated with polysomnography for patients with OSAS. Subjects were 10 patients (51.7+/-19.0 years old). The average ESS and MSLT scores were 10.6+/-5.6 and 7.7+/-5.6, respectively. There was no significant relationship between ESS and MSLT. The Multiple Sleep Latency Test had a significant negative relationship with the number of awakenings and the apnea/hypopnea index. No relationship was found between nocturnal hypoxia and either ESS or MSLT. Our findings suggest that objective EDS in OSAS is related with fragmentation of sleep, and that several patients are not aware of their EDS.

Adult↗

PubMed1999

Polysomnographic and urodynamic changes in a case of obstructive sleep apnea syndrome with enuresis.

A 53-year-old female patient with obstructive sleep apnea syndrome was reported. She had complained of enuresis as well as a 15-year history of snoring, but she had no complaint of sleep and awake disturbance. Polysomnographic study showed repeated obstructive apnea and hypopnea with an apnea/hypopnea index of 52.6, and severe oxygen desaturation during sleep. On cystometography during sleep, the changing amplitude of the spike wave corresponds to the changes of respiratory efforts against a closed upper airway. The patient was treated successfully with imipramine and acetazolamide for the obstructive sleep apnea and enuresis. Apnea/hypopnea index, nocturnal oxygen desaturation, and sleep architecture were improved, and enuresis completely disappeared. Cystometrography during sleep showed that the average amplitude of the spike wave tended to be low. Percentage urinary volume during sleep compared with 24 h volume was significantly reduced. We considered that the enuresis was mainly related to increased intra-abdominal pressure produced by respiratory efforts and enhanced nocturnal urine production.

Acetazolamide↗

PubMed1999

Esophageal undifferentiated carcinoma displaying marked chondroid differentiation at metastatic foci.

A report of an unusual esophageal tumor in an 81-year-old man is presented. The primary tumor was diagnosed as undifferentiated carcinoma at biopsy and had disappeared after irradiation treatment. However, multiple metastases were noted in the brain, lungs, kidneys, adrenals and spleen at autopsy. Histologically, metastases showed marked cartilaginous metaplasia as demonstrated by light microscopy, histochemical and immunohistochemical studies, although the initial biopsy sample did not possess chondroid matrix. Furthermore, an apparent transition could be traced from carcinomatous to chondroid cells, suggesting that the chondroid cells were derived from carcinoma cells. The carcinomatous area partially showed both squamous and glandular differentiation, although they were poorly differentiated. A retrospective immunohistochemical study that used a panel of antibodies suggested a phenotypic relevance between primary and metastatic tumors.

Aged↗

PubMed1999

H+/K+-adenosine triphosphatase mRNA in gastric fundic gland mucosa in patients infected with Helicobacter pylori.

BACKGROUND: How Helicobacter pylori infection affects gastric acid secretion has not been made clear. This study aimed to elucidate the effects of H. pylori infection on H+/K+-adenosine triphosphatase (ATPase) mRNA in gastric fundic gland mucosa. METHODS: Twenty patients with chronic gastritis and H. pylori infection were treated with lansoprazole and antibiotics. Before and 1 month after treatment gastroduodenoscopy was performed, and changes in the amount of H+/K+-ATPase mRNA in the fundic gland mucosa, gastric juice pH, and serum gastrin levels were determined. RESULTS: The amount of H+/ K+-ATPase mRNA in the fundic gland mucosa was increased in patients with eradication of H. pylori, in whom significant decreases in gastric juice pH and serum gastrin levels were observed. No significant changes were observed in patients without eradication of H. pylori. CONCLUSIONS: These results suggest that one of the mechanisms by which H. pylori infection suppresses acid secretion is by the inhibition of proton pump synthesis in parietal cells.

DNA Primers↗

PubMed1999

Complete inhibition of mouse macrophage-derived foam cell formation by triacsin C.

Primary mouse peritoneal macrophages effectively take up and metabolize phosphatidylcholine/cholesterol liposomes containing a small amount of phosphatidylserine, which results in the massive accumulation in the cytoplasm of oil red O positive lipid droplets consisting of cholesteryl ester (CE) and triacylglycerol (TG) [Nishikawa et al. (1990) J. Biol. Chem. 265, 5226-5231]. A number of inhibitors of CE synthesis have been reported, but their effects on the lipid droplet formation have not been fully examined. Furthermore, the contribution of TG synthesis to lipid droplet formation has been poorly investigated. We have investigated the relationship between CE and TG syntheses and cytosolic lipid droplet formation in macrophages cultured in the presence of inhibitors with different modes of action. When macrophages were cultured with liposomes and [14C]oleic acid in the presence of triacsin C, a potent inhibitor of long chain acyl-CoA synthetase, both [14C]CE and [14C]TG syntheses were inhibited to similar extents with IC50 values of 0.19 and 0.10 microM, respectively. On the other hand, pregnenolone, a well-known inhibitor of cellular cholesterol transport, and CL-283,546, a potent inhibitor of acyl-CoA:cholesterol acyltransferase, inhibited [14C]CE synthesis specifically with IC50 values of 5.0 and 0.038 microM, respectively. Microscopic observation revealed that the inhibitors of cholesterol metabolism produce only a partial decrease in cytosolic lipid droplets even at the highest doses which cause almost complete inhibition of [14C]CE synthesis. However, the triacsin C-dose dependent inhibition of lipid droplet formation was almost complete at 0.59 microM, a concentration that inhibits [14C]CE and [14C]TG syntheses by about 90%. These results show that inhibiton of acyl-CoA synthetase by triacsin C causes a decrease in the cellular levels of acyl-CoA, the common substrate for CE and TG syntheses, leading to an inhibiton of neutral lipid synthesis and eventually to the complete disappearance of cytosolic lipid droplets from macrophages. These findings suggest that TG synthesis, as well as CE synthesis, is responsible for macrophage-derived foam cell formation, and is therefore a potential target for new antiatherosclerotic agents.

Animals↗

PubMed1999

Probing the substrate specificity of the intracellular brain platelet-activating factor acetylhydrolase.

Platelet-activating factor acetylhydrolases (PAF-AHs) are unique PLA2s which hydrolyze the sn-2 ester linkage in PAF-like phospholipids with a marked preference for very short acyl chains, typically acetyl. The recent solution of the crystal structure of the alpha(1) catalytic subunit of isoform Ib of bovine brain intracellular PAF-AH at 1.7 A resolution paved the way for a detailed examination of the molecular basis of substrate specificity in this enzyme. The crystal structure suggests that the side chains of Thr103, Leu48 and Leu194 are involved in substrate recognition. Three single site mutants (L48A, T103S and L194A) were overexpressed and their structures were solved to 2.3 A resolution or better by X-ray diffraction methods. Enzyme kinetics showed that, compared with wild-type protein, all three mutants have higher relative activity against phospholipids with sn-2 acyl chains longer than an acetyl. However, for each of the mutants we observed an unexpected and substantial reduction in the V(max) of the reaction. These results are consistent with the model in which residues Leu48, Thr103 and Leu194 indeed contribute to substrate specificity and in addition suggest that the integrity of the specificity pocket is critical for the expression of full catalytic function, thus conferring very high substrate selectivity on the enzyme.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1999

Microanatomy of the cerebellopontine angle and internal auditory canal: study with new magnetic resonance imaging technique using three-dimensional fast spin echo.

OBJECTIVE: We report a new magnetic resonance imaging technique that uses three-dimensional fast spin echo and the minimum intensity projection method. Using this technique, detailed images of the cerebellopontine angle (CPA) and internal auditory canal (IAC) were obtained in normal volunteers and in patients with acoustic neuromas or hemifacial spasm. METHODS: Ten normal volunteers, 44 patients with acoustic neuromas, and 31 patients with hemifacial spasm were studied using the three-dimensional fast spin echo magnetic resonance imaging protocol. The CPA and IAC were scanned by using a 1-mm slice thickness in the axial and parasagittal planes. RESULTS: Normal anatomy was as follows. 1) The vestibulocochlear nerve was ovoid near the brain stem and changed to a slightly crescentic configuration (C shape) as it traveled laterally. 2) Separation of the cochlear and vestibular nerves was observed near the central part of the IAC. 3) Discrimination between the superior and inferior vestibular nerves was also possible near the fundus of the IAC. 4) The facial nerve was easily identifiable as a discrete nerve at the anterior aspect of the vestibulocochlear nerve. 5) The meatal loop of the cerebellar artery was located medial to the porus in 44% of 95 CPAs and reached the porus or protruded into the porus in 56%. Acoustic neuromas were as follows. 1) In a patient with a very small intracanalicular tumor, the nerve on which the tumor was located could be identified. 2) In 22 of 44 acoustic neuromas, cerebrospinal fluid was present between the tumor and the fundus of the IAC. Hemifacial spasm was as follows. The relationship between the responsible artery and the facial nerve could be precisely observed. CONCLUSION: The three-dimensional fast spin echo method offers ultrahigh-resolution images, which are extremely useful in understanding the surgical anatomy of the CPA and IAC.

Cerebellopontine Angle↗

PubMed1999

Genetic association between cytochrome P-450 2D6 gene polymorphism and plasma concentration of haloperidol in Japanese schizophrenics.

Haloperidol is one of the major neuroleptics partly metabolized by cytochrome P-450 2D6 (CYP2D6), which has over 10 genetic polymorphisms. The purpose of this study was to investigate whether individual haloperidol plasma concentration was affected by CYP 2D6 gene polymorphisms. The genomic DNA of 56 subjects who have been taking haloperidol were analysed by restriction fragment length polymorphism (RFLP) method to detect the major Caucasian mutations, CYP 2D6A, 2D6B, and the major oriental population mutation, 2D6J. We found 10 cases of the CYP 2D6J mutation, only one case of the CYP 2D6B mutation, and no cases of the CYP 2D6A mutation in the present subjects. Contrary to expectations, haloperidol plasma concentration of the CYP 2D6B mutation case showed a lower haloperidol plasma concentration than the mean value of that of wild type homozygous cases. Haloperidol plasma concentration of 10 subjects who had the CYP 2D6J mutation cases showed no significant difference from that of the wild type homozygous group. These results suggest that the major genetic polymorphisms of CYP 2D6 do not seem to be one of the factors which affect individual haloperidol plasma concentration in Japanese schizophrenics.

Adult↗

PubMed1999

Genetic organization and characteristics of the 3-(3-hydroxyphenyl)propionic acid degradation pathway of Comamonas testosteroni TA441.

Comamonas testosteroni TA441 degrades 3-(3-hydroxyphenyl)propionate (3HPP) via the meta pathway. A gene cluster required for degradation of 3HPP was cloned from strain TA441 and sequenced. The genes encoding six catabolic enzymes, a flavin-type hydroxylase (mhpA), extradiol dioxygenase (mhpB), 2-keto-4-pentenoate hydratase (mhpD), acetaldehyde dehydrogenase (acylating) (mhpF), 4-hydroxy-2-ketovalerate aldolase (mhpE) and the meta cleavage compound hydrolase (mhpC), were found in this cluster, encoded in this order. mhpD and mhpF were separated by two genes, orf4 and orf5, which were not necessary for growth on 3HPP. The gene mhpR, encoding a putative transcriptional activator of the IcIR family, was located adjacent to mhpA in the opposite orientation. Disruption of the mhpB or mhpR genes affected growth on 3HPP or trans-3-hydroxycinnamate. The mhpB and mhpC gene products showed high specificity for 3-(2,3-dihydroxyphenyl)propionate (DHPP) and the meta cleavage compound produced from DHPP, respectively.

Aldehyde Oxidoreductases↗