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Biomedical subjects

M Arai

Publications and source records attributed to M Arai.

At least 343 records · Page 19Linked to original sources

Influence of myopic refraction on visual field defects in normal tension and primary open angle glaucoma.

It is known that the prevalence of normal tension glaucoma (NTG) or primary open angle glaucoma (POAG) is higher in the myopic population and that the prevalence of myopia and NTG is higher in Japan than in western countries. To evaluate the influence of myopic refractive error in the central 10 degrees of the visual field in NTG eyes, the data obtained from NTG eyes with the Humphrey Visual Field Analyzer were analyzed in comparison with data from POAG eyes. One hundred and twenty eyes of 86 NTG patients and 197 eyes of 138 POAG patients whose ages were 65 years or younger were included in this study. All of them had clear ocular media, refractive power less than +1.0 diopter and no myopic degeneration in the fundus. Multiple linear regression analysis was performed with the dependent variable of the deviation of the measured threshold value from the normal reference value (TD; STATPAC 2), and independent variables of myopic refractive power and the mean deviation (MD; STATPAC 2) as an index of the disease stage at each test point of the Humphrey 10-2 program and at the most central 12 test points of the 30-2 program. Myopic power was found to have a significant positive correlation with the depression in the lower cecocentral area in both NTG and POAG eyes, while only in NTG eyes it had a significant negative correlation with the depression in the upper arcuate area extending just nasal to the fixation point.

Aged↗

[Usefulness of thin axial images of computerized tomography angiography for surgery on paraclinoidal carotid artery aneurysms].

A number of surgical experiences with paraclinoidal carotid artery aneurysms have been reported recently. However, neuroradiological examinations can not sufficiently visualize the topographic relations around the aneurysms due to variations in the size of the anterior clinoid process (ACP) or course of the carotid artery in individual cases. Although three-dimensional computerized tomography angiography (3-D-CT-A) is known to be useful for the surgical management of cerebral aneurysms in common locations, its usefulness for paraclinoidal carotid artery aneurysms has not been investigated. Ten cases involving a total of 13 aneurysms located in the clinoid portion of the carotid artery were included in this study according to Al-Radham's classification (Table). The CT scan used was an X Force system manufactured by Toshiba Electric Co, Japan. Non-ionic, iodinated contrast solution, a total of 2ml/kg, was intravenously infused at a rate of 2ml/sec. Helical scanning was begun 30 seconds after initiating the infusion, 1mm pitch/1.5 second/rotation. 3-D images and original images of axial slices were compared to conventional angiography, DSA and surgical findings. The 3-D images of 3-D-CT-A was able to demonstrate both aneurysms located in the C2 segment of the carotid artery (groups I and II), and five of nine carotid cave aneurysms (group III). The aneurysms located more proximally (group IV or V) could not be visualized.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case of thrombocytopenia due to heparin therapy for a progressing ischemic stroke].

A 44-year-old man was admitted, complaining of weakness of his left limbs. On admission, he was oriented and cooperative. He showed positive Barré sign only on the left leg. Deep tendon reflexes were unremarkable; pathological reflexes were negative. There was no cerebellar ataxia or sensory deficit. Immediately after admission, monoplegia of the left leg progressed. He was started on heparin infusion therapy. His paralysis had been resolved by the 5th day. MRI of the brain demonstrated an infarction involving the body of the corpus callosum, the right cingulate gyrus, and the right paracentral lobule. Neuropsychologic examination demonstrated a disturbance of interhemispheric transfer of position. On the 10th day he developed Klebsiella ozaenae bacteremia. On the 11th day, platelet count was 9.2 x 10(4)/microliter. Antithrombin III, thrombin antithrombin III complex, D-dimer, and FDP levels were unremarkable, which is quite atypical for DIC associated with bacterial infection. Platelet factor 4 and beta-thromboglobulin levels were remarkably high, suggesting activated platelet aggregation. We made a diagnosis of heparin-induced thrombocytopenia and discontinued heparin infusion. Three days later, platelet count began to increase and creatinine levels returned normal. All patients receiving heparin should be monitored for platelet count.

Adult↗

[Wallenberg's syndrome following minor neck trauma: a case associated with atlanto-axial subluxation, an anomaly of the axis, and platelet activation].

A 38-year-old man hit his forehead against a steel pipe, which made his neck hyperextended. He noticed unsteady gait and dysphagia approximately 6 hours after the accident. On the next day he was admitted. He had a Horner's syndrome, and pharyngeal and palatal weakness on the right side. There were no pyramidal tract signs. He could not balance on his right foot or gait tandemly. Sensation for cold and pin-prick was absent on his left limbs; position sense was intact. Angiography demonstrated an occlusion of the right vertebral artery at the 3rd segment. Cranial MRI demonstrated an infarction in the right lateral medulla. A radiogram demonstrated an atlanto-axial instability. There was an anomalous bone mass between the left superior articular process and the odontoid process. These abnormalities might have precipitated injury of the vertebral artery during the minor neck trauma. The plasma levels of molecular markers for coagulation and fibrinolysis were unremarkable. In contrast, beta-thromboglobulin and platelet factor 4 levels were high, suggesting activated platelet aggregation. To my knowledge, this is the first report showing evidence for platelet activation at the molecular level early in the course of vertebral artery thrombosis following a minor neck trauma.

Adult↗

[Alteration of drinking pattern after the entrance of university].

Three hundred fifty-nine freshmen and freshwomen of Tokai University and Tamagawa University were examined for alcohol habituelle using questionnaires on life style and club activity as well as the established questionnaires of the Adolescent Alcohol Involvement scale (AAIS). The scores of AAIS of the male and female students were 30.6 and 27.7, respectively. About 10% of the subjects were revealed to be alcohol misusers. In both sexes, the drinking patterns remarkably changed after the entrance of university. Even in females, the drinking pattern markedly changed. The grade of club activity is one of factors influencing the drinking pattern of students. Especially big changes were observed in the students of cultural clubs.

Adult↗

Heterogeneous expression of glycoprotein Ib, IX and V in platelets from two patients with Bernard-Soulier syndrome caused by different genetic abnormalities.

Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder, which is caused by deficiency or decrease of the platelet GPIb/IX/V complex. Analysis of two patients with BSS by flow cytometry of the blood revealed different expression patterns of the components of the GPIb/IX/V complex. In case 1, GPIX was completely absent but residual amounts of GPIb alpha and GPV were detectable; in case 2, GPIb alpha was completely absent. We amplified the coding regions of GPIb alpha, GPIb beta, GPV, and GPIX from the patients' genomic DNA with the polymerase chain reaction (PCR) and sequenced the PCR products. in case 1, we identified a point mutation in the GPIX coding region that changes the codon for tryptophan-126 (TGG) to a nonsense codon (TGA). In case 2, we found a deletion of nucleotide within seven adenine repeats at the position of 1932 to 1938 in the coding region of GPIb alpha, which causes a frame shift that results in 58 altered amino acids and a premature stop codon. These genetic changes alter the transmembrane domain of GPIX or GPIb alpha and, therefore, would prevent proper insertion of the proteins in the plasma membrane. Thus, abnormality of a single component protein (GPIX or GPIb alpha) alters the assembly of the GPIb/IX/V complex and causes heterogeneous surface expression of GPIb alpha, GPV and GPIX.

Adult↗

Role of neutrophil-endothelial cell interactions in gastric mucosal injury induced by aspirin.

Recent studies have indicated that aspirin promotes neutrophil adherence to endothelium via CD11/CD18-dependent interactions with intercellular adhesion molecule 1, which subsequently leads to neutrophil-mediated cell injury. The objectives of the present study were to determine the role of neutrophil-endothelial cell interactions and lipid peroxidation in aspirin-induced gastric mucosal injury in rats. Oral administration of aspirin and HCl produced hemorrhagic erosions in the stomach of rats. Myeloperoxidase (MPO) activity in the gastric mucosa, an index of neutrophil infiltration, significantly increased 3 h after aspirin administration. The concentration of thiobarbituric acid-reactive substances (TBA-RS) in the gastric mucosa, an index of lipid peroxidation, increased slightly 3 h after aspirin administration. In rats treated with antineutrophil serum, both the total area of gastric erosions and MPO activity were significantly reduced. In addition, pretreatment with anti-CD18 monoclonal antibodies significantly attenuated gastric mucosal damage and inhibited the increases in both MPO activity and TBA-RS in the gastric mucosa after aspirin administration. These observations suggest that CD18-dependent neutrophil-endothelial cell interactions and lipid peroxidation play an important role in the pathogenesis of gastric mucosal lesions induced by aspirin.

Animals↗

Effects of oxygen radical scavengers on the quality of gastric ulcer healing in rats.

Oxygen free radicals have been implicated in the pathogenesis of gastrointestinal mucosal injury. However, their effect on the quality of experimental gastric ulcer healing has not been investigated previously. Gastric ulcers were produced on the anterior wall of the stomach of rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcers were treated with scavengers for 6 weeks. Rats received either a daily dose of 20,000 U/kg of recombinant human Cu,Zn-SOD, a 1% solution of DMSO administered orally ad libitum, or 50 mg/kg/day of allopurinol administered orally. The quality of ulcer healing was evaluated by histologic and biochemical parameters: ulcer area, lipid peroxide levels, abnormality of regenerated mucosa, angiogenesis, and fibrosis as assessed by Azan staining, mucin content as assessed by the PAS-positive area, and polymorphonuclear leukocyte (PMN) infiltration. The treatments with SOD, DMSO, or allopurinol did not affect the ulcer area or lipid peroxide levels in the gastric mucosa, and SOD did not affect the histologic abnormality score, PMN infiltration in regenerated mucosa, the collagen fiber proliferation index, or the PAS-positive mucous score. DMSO and allopurinol significantly increased the collagen fiber proliferation index and the PAS-positive mucous score compared with controls. These results indicate that scavenging hydroxyl radicals or inhibiting xanthine oxidase enhances the quality but not the speed of gastric ulcer healing.

Animals↗

Crystallization and preliminary X-ray diffraction studies of an endoglucanase from Aspergillus aculeatus.

Most fungal cellulases are found in multiple forms varying in size and substrate specificity. Aspergillus aculeatus is known to produce nine cellulolytic enzymes including an endoglucanase (FI CM-cellulase, M(r) = 24,002) as the major component. Single crystals of FI CM-cellulase from Aspergillus aculeatus have been prepared by sitting-drop vapour diffusion using ammonium sulphate as a precipitant. The cellulase crystals belong to the orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions of a = 52.79(2) A, b = 106.40(4) A and c = 33.15(1) A. The crystals contain one enzyme molecule per asymmetric unit. They diffract to at least 2.0 A resolution and are very stable against X-ray irradiation.

Ammonium Sulfate↗

Subcellular localization of the F5 protein to the neuronal membrane-associated cytoskeleton.

F5 was identified originally as an interleukin-2-regulated gene in the murine helper T-lymphocyte clone L2. Subsequent studies demonstrated high levels of F5 mRNA and protein in mature neurons in adult mouse central and peripheral nervous systems. The F5 protein was present in dendrites and perikarya but not in axons. In the present studies, the intracellular localization of the F5 protein in adult mouse brain was determined by subcellular fractionation and Western blotting. Although the deduced F5 sequence predicts a soluble protein, virtually no F5 immunoreactivity was found in the cytosol. The F5 protein was restricted to the P2 crude mitochondrial and P3 crude microsomal particulate fractions. Within the P2 fraction, F5 protein was enriched in the P2B synaptosomal subfraction. The results of temperature-dependent phase separation with Triton X-114 and alkaline extraction with sodium carbonate of the P2 and P3 fractions were consistent with the F5 protein being an extrinsic membrane-associated protein. Although essentially all of the F5 protein in the P3 fraction was membrane-associated, a substantial proportion of P2-associated F5 protein and nearly all of the synaptosomal F5 protein was detergent-insoluble. Direct isolation and subfractionation of brain cytoskeleton confirmed colocalization of F5 immunoreactivity with the membrane-associated cytoskeleton and postsynaptic densities. These studies suggest that the F5 protein, which has a large number of potential phosphorylation sites, plays a role in membrane-cytoskeletal interactions and in dynamic aspects of synaptic structure or function.

Animals↗

Cloning and activation of the Syrian hamster neu proto-oncogene.

Point mutations of the Syrian hamster neu proto-oncogene have been observed in the transmembrane domain of N-nitroso-N-ethylurea (ENU)-induced neurofibromas. Genomic DNA derived from tumor tissue showed transforming activity in an NIH 3T3 assay and a cDNA clone of the hamster neu gene, containing the entire protein-coding region, was isolated from a transformant cDNA library. The encoded product is 92 and 88% homologous to the rat neu and the human c-erbB-2, respectively. The product of the mutated hamster neu gene showed increased autophosphorylation of Tyr residues.

3T3 Cells↗

Motor neuron disease with multi-system involvement presenting as tetraparesis, ophthalmoplegia and sensori-autonomic dysfunction.

We carried out a postmortem examination on two Japanese patients, 64- and 80-year-old men whose survival was prolonged with an artificial respirator. They had no family history of neuropsychiatric disorders and were suspected, clinically, as having a motor neuron disease that differed from amyotrophic lateral sclerosis (ALS). As well as upper and lower motor neuron impairment, they showed a variety of symptoms, such as sensory disturbances, hypohidrosis, impotence, ophthalmoparesis and/or atonic neurogenic bladder, and their protein content in cerebrospinal fluid was elevated markedly. Pathological examination revealed the following extensive nervous system involvement: (1) the upper and lower voluntary motor systems, including the IIIrd, IVth and VIth cranial nerve nuclei: (2) the reticular formation and its major afferent pathways; (3) the vestibulospinal and tectospinal systems; (4) the spinocerebellar system and the exteroceptive somatic afferent pathways; (5) the dentatorubral and pallidoluysian systems; and (6) the substantia nigra, locus ceruleus and intermediolateral and Onufrowicz's nuclei. Neither Bunina bodies, Lewy body-like hyaline inclusions nor ubiquitin immunoreactive skein-like structures were observed. The distribution of the lesions was quite different from that in patients with ALS and the other known related diseases. Recently, seven autopsied cases with clinical and histopathological similarities to our patients have been reported in Japan. Our conclusion is that our two and these seven patients should be classified as having a new motor neuron disease entity, which can be is differentiated from ALS.

Aged↗

Fat-storing cell abnormalities associated with endothelial cell damage after cold ischemic storage of rat liver in UW solution.

Rat liver was stored at 1 degree C in University of Wisconsin solution, and morphological changes were observed after 12, 18, 24, and 36 hr by transmission electron microscopy. There were two types of endothelial cell damage in the hepatic sinusoids. One was disruption of the endothelial linings, and the other detachment of endothelial cells into the sinusoidal space accompanied by fat-storing cell abnormalities. The former damage was seen after storage longer than 12 hr, while the latter developed after 18 hr even in the hepatic sinusoids with no disruption of the linings. Considering that fat-storing cell damage can produce endothelial cell destruction, this damage should be given attention as one of factors of endothelial cell destruction in the hepatic sinusoids after cold storage of the liver.

Adenosine↗

Gene expression of interstitial collagenase (matrix metalloproteinase 1) in gastrointestinal tract cancers.

Collagenolytic proteinases play an important pathological role in the invasion and metastasis of cancer cells. However, little is known about the role of interstitial collagenase (matrix metalloproteinase-1; MMP-1) in this process. To investigate the expression of the MMP-1 gene in cancer tissues, an in situ hybridization study was carried out in gastrointestinal tract cancers (one esophageal cancer, five gastric cancers, and four colorectal cancers), using a 35S-labeled MMP-1 cDNA probe. The MMP-1 gene was expressed in the stromal cells of fibrous tissue around cancer nests, especially at the margin of invasion and/or within the cancer nest; however, no definite expression within cancer cells was observed. Expression of the MMP-1 gene in the stromal cells was more common in well differentiated gastric adenocarcinoma than in poorly differentiated adenocarcinomas. These findings indicate that expression of the MMP-1 gene is greater in stromal cells that are closely associated with cancer cells, suggesting a pathophysiological role of MMP-1 in the invasion and metastasis of cancer cells.

Adenocarcinoma↗

An important role of heparan sulfate proteoglycan (Perlecan) in a model system for the deposition and persistence of fibrillar A beta-amyloid in rat brain.

A consistent rat model for the study of the consequences of congophilic and fibrillar A beta-amyloid in brain has been developed. One hundred percent of animals receiving infusions of synthetic beta-amyloid protein (A beta 1-40) plus a specific heparan sulfate proteoglycan (HSPG) for 1 week or 7 weeks (following 2 week infusions) demonstrated Congo red and thioflavin S-positive deposits adjacent to the infusion site. Extracellular amyloid fibrils were identified by electron microscopy and were immunogold decorated with A beta antibody. Significant increases in Congo red staining were observed in animals infused with A beta plus HSPG versus those infused with only A beta. Infusion of A beta alone was variable with respect to congophilic amyloid persistence, which occurred in 50% of animals and only when endogenous HSPGs accumulated at A beta deposition sites. By 7 weeks, only animals infused with A beta plus HSPG demonstrated compaction of the Congo red material from amorphous, wispy deposits (at 1 week) to stellate deposits resembling a Maltese cross. These spherical amyloid deposits were very similar to Congo red-stained amyloid plaques in human Alzheimer's disease brain, and in vitro data suggest that they were probably formed in vivo following interactions with endogenous brain components.

Amyloid beta-Peptides↗

Immunohistochemical analysis of perforin and granzyme A in inflammatory myopathies.

Perforin (PF) and granzyme A (GA) are candidates suspected of being cytolytic proteins of the granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. We analysed PF and GA in muscles from patients with inflammatory myopathies. Five cases of polymyositis (PM), two cases of inclusion body myositis (IBM), and five cases of dermatomyositis (DM) were studied immunohistochemically using anti-PF and GA antibodies raised against each synthetic peptide of human PF and mouse GA, together with a panel of monoclonal antibodies reactive for lymphocyte subsets. In PM and IBM, PF positive cells were colocalized with GA positive cells and occasionally invaded into the non-necrotic muscle fibres. The percentage of PF positive cells among the endomysial CD8 positive cell population was 9.9% (PM) and 12.5% (IBM), and the majority of the endomysial CD8 positive cells were alpha/beta T cells. In contrast, in DM, both PF and GA positive cells were very few in all cases. Only few inflammatory cells were CD16+ or CD57+ NK cells among these diseases. Our results suggest that PF and GA are secreted mainly from alpha/beta T cells, and may play a key role in muscle fibre damage in at least some PM and IBM, but not in DM.

Aged↗

New teleocidin-related metabolites, (-)-7-geranylindolactam V and blastmycetin F, from Streptoverticillium blastmyceticum.

Two new teleocidin-related metabolites, (-)-7-geranylindolactam-V [2] and blastmycetin F [3], were isolated from fermentation broths of the actinomycete Streptoverticillium blastmyceticum NA34-17, and their structures were determined by spectroscopic methods. Compound 2 bound strongly to phorbol ester receptors in a mouse epidermal particulate fraction, suggesting that it is a potent in vivo tumor promoter comparable to teleocidins A-1 [4] and B-4 [5].

Animals↗

DNA adduct formation and assessment of aberrant crypt foci in vivo in the rat colon mucosa after treatment with N-methyl-N-nitrosourea.

N-Nitroso-compound DNA adduct formation in vivo and occurrence of aberrant crypt foci (ACF) were studied in the rat colon mucosa after a single, local treatment with a carcinogen, N-methyl-N-nitrosourea (MNU), using a simple surgical approach. A segment of F344 rat colon was ligated to make a pouch and injected with MNU solution. For the study of DNA adduct formation, the solution contained 50 microCi of [3H]MNU. The results demonstrated that similar ranges of carcinogen dose, i.e. 0.15 x 10(-2) - 1.5 x 10(-2) M MNU, could induce both DNA adduct formation and appearance of ACF in the rat colon with both parameters showing a nearly linear dose dependence. HPLC analysis revealed the DNA adducts to include both 7-methylguanine (7-mGua) and O6-methylguanine (O6-mGua) with the 7-mGua/O6-mGua ratio being 8.2-11.3:1 in the system used. Assessment of ACF development from 4 to 16 weeks after MNU treatment at a dose of 7.5 x 10(-2) M showed the numbers to increase up to the 8th week, followed by a decrease at weeks 12 and 16, when 40% of the ACF counted at the peak time point were still present. The percentage of large ACF (> or = 4 crypts/ACF) significantly increased with time. These results indicate a clear relation between DNA adducts and preneoplastic lesions, i.e. ACF. In conclusion, DNA adduct formation and ACF can be efficiently and simply detected in vivo by using the method described in the present paper.

Animals↗