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Biomedical subjects

M Arai

Publications and source records attributed to M Arai.

At least 271 records · Page 15Linked to original sources
PubMed1996

Inhibition of TGF-beta 1 expression by antisense oligonucleotides suppressed extracellular matrix accumulation in experimental glomerulonephritis.

Overproduction of transforming growth factor-beta 1 (TGF-beta 1) has been implicated in the pathogenesis of fibrotic diseases. TGF-beta 1 plays a crucial role in the accumulation of extracellular matrix (ECM) in human and experimental glomerular diseases. However, it remains unclear whether inhibition of TGF-beta 1 overproduction would suppress TGF-beta 1-induced ECM accumulation. To inhibit the overproduction of TGF-beta 1 in experimental glomerulonephritis induced by anti-Thy 1.1 antibody, we introduced antisense oligodeoxynucleotides (ODN) for TGF-beta 1 into the nephritic kidney by the HVJ-liposome-mediated gene transfer method. Sense, scrambled or reverse ODN were also introduced as controls. Transfected ODN accumulated mainly in the nuclei of mesangial cells in the glomeruli of transfected kidneys. In the antisense ODN-transfected rats, a marked decrease in expression of TGF-beta 1 mRNA was confirmed by Northern analysis. Consequently, the expression of TGF-beta 1 protein in the glomerulus was markedly reduced in the antisense ODN-transfected kidney with a comparable effect in preventing glomerular ECM expansion in experimental glomerulonephritis. In contrast, sense, scrambled and reverse ODNs failed to suppress TGF-beta 1 expression and ECM accumulation. Thus, these results suggested that inhibition of TGF-beta 1 overproduction could suppress progression to glomerulosclerosis.

Animals↗
PubMed1996

Role of adhesion molecules in the development of massive hepatic necrosis in rats.

Massive hepatic necrosis develops after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes as a result of microcirculatory disturbance caused by endothelial cell destruction by activated macrophages in the hepatic sinusoids. Immunohistochemical hepatic expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen 1 alpha (LFA-1 alpha) and the effect of monoclonal antibodies against both adhesion molecules on liver necrosis provoked after endotoxin administration was studied in these rats. There were increased stains of ICAM-1 in endothelial cells and LFA-1 alpha in macrophages in the hepatic sinusoids in Propionibacterium acnes-pretreated rats compared with normal rats. Such stains were further increased soon after endotoxin administration, followed by development of hepatic necrosis. Monoclonal antibodies against both adhesion molecules significantly attenuated the extent of liver injury compared with controls, without affecting the infiltration and activation of hepatic macrophages. Polyclonal antibodies against polymorphonuclear leukocytes eradicated circulating neutrophils, but did not change such liver injury, although gum arabic, which suppressed macrophage activation, attenuated the extent of liver injury. Thus, adhesion between endothelial cells and activated macrophages in the hepatic sinusoids via ICAM-1 and LFA-1 alpha is essential for the initiation of massive hepatic necrosis of this type. Contribution of neutrophils seems less likely.

Animals↗
PubMed1996

Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hapatocellular-cholangiocellular carcinomas.

Because combined hepatocellular-cholangiocellular carcinoma is rare and its biological features and pathogenesis have not been well established, we investigated alterations of the p53, K-ras and Rb-1 genes, as well as expression patterns of carcinoembryonic antigen and keratin, in seven combined hepatocellular-cholangiocarcinomas out of 557 hepatocellular carcinomas autopsied at Tokyo University during 30 years. Mutations of the p53 gene were found in two cases, at codon 244 (GGC to TGC) in the cholangiocellular carcinoma component of case 1 (mixed type, showing an intimate intermingling of both elements) and at codon 234 (TAC to AAC) in both components of case 5 (combined type, consisting of contiguous but independent masses of both elements). Mutation of the K-ras gene (codon 12, GGT to GAT) was seen only in the cholangiocellular carcinoma component of clinically apparent double cancer, case 6. Allelic alteration of the Rb-1 gene was observed in two cases, deletion of both alleles in the hepatocellular carcinoma component of case 3 (combined type) and replication error of the same pattern in both components of case 4 (mixed type). Immunohistochemical analysis showed that the hepatocellular carcinoma components of five cases (cases 2, 3, 5, 6, 7) were immunoreactive for keratin, suggesting biliary epithelial transformation. In four of the five cases (cases 3 and 5 combined, case 7 mixed and case 6 double cancer), cholangiocellular carcinoma components were also positive for keratin. These results suggest that both components of combined hepatocellular-cholangiocarcinoma have the same genetic and phenotypic character and might have arisen from the same origin in some cases.

Aged↗
PubMed1996

Spatial tuning loss of pattern reversal visual evoked response in optic nerve disease.

We compared the pattern reversal visual evoked response (PVER) amplitude-check size functions from 25 eyes (25 normal subjects; visual acuities > or = 20/20) with those from 32 eyes (22 patients; visual acuities 20/15 to 20/50; mean, 20/25.5) with mild optic nerve disease to determine if spatial tuning loss of the PVER occurs in the presence of optic nerve dysfunction. The steady-state PVER was recorded with five check sizes (range, 160 to 10 minutes of arc). To analyze the PVER amplitude-check size function, we calculated the difference between the maximum and minimum PVER amplitudes and then calculated the area of spatial tuning (the area under the function). Values were significantly smaller in patients than in normal subjects (1.81 +/- 1.27 microV versus 5.73 +/- 3.27 microV; F = 41.24, p = 0.0001; 3.87 +/- 2.70 area units versus 12.57 +/- 7.60 area units; F = 38.62, p = 0.0001). There was no shift in the distribution of peak check sizes. Results suggest that a spatial tuning loss occurs in optic nerve disease. The shape of the function, including the area of spatial tuning, appears to be a sensitive indicator of early or mild optic nerve dysfunction.

Adolescent↗
PubMed1996

Susceptibility of mice to bacterial and fungal infections after intragastric administration of ebselen.

The seleno-organic compound ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) has anti-inflammatory activity and exhibits glutathione peroxidase-like activity in-vitro. Ebselen inhibited candidacidal activity over the same range of concentrations as it inhibited the production of microbicidal H2O2 by human neutrophils and macrophage-like cells. Therefore, the long-term administration of ebselen might be expected to induce an immunocompromised state in the host. To examine such a possibility, mice (5-weeks-old ddY, male) were given daily intragastric doses of 0, 10 or 100 mg/kg-1 ebselen for 21 days and then infected intraperitoneally with Candida albicans (10(8) cells/mouse), Pseudomonas aeruginosa (1.5 x 10(7) cells/mouse) or methicillin-resistant Staphylococcus aureus (5 x 10(8) cells/mouse). Ebselen at none of the tested doses affected the increase in body weight of mice during administration of the drug. No evidence was obtained that mice became more susceptible to the various microorganisms after the administration of ebselen at any tested dose.

Animals↗
PubMed1996

Factors modifying protective effect of anti-CD18 antibodies on myocardial reperfusion injury in dogs.

Anti-CD18 monoclonal antibodies (MAb) have demonstrated variable protection against neutrophil (PMN)-mediated myocardial reperfusion injury. To identify factors contributing to this variability, open-chest dogs underwent coronary artery occlusion for 90 min followed by reperfusion for 3.5 h. Ten minutes before reperfusion the dogs received saline (n = 18) or one of three anti-CD18 MAb: MHM.23, R15.7, or PLM-2 (2, 1, and 1 mg/kg and n = 19, 8, and 4, respectively). Collateral flow was measured with radioactive microspheres, area at risk was assessed with monastral blue dye, and infarct size was measured postmortem by triphenyltetrazolium chloride. In vitro, all three MAb bound to canine PMNs, but only MHM.23 and R15.7 inhibited their adherence to keyhole limpet hemocyanin-coated plastic. In vivo, only MHM.23 and R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow. MHM.23 afforded protection in dogs with moderate ischemia (epicardial collateral flow > 0.1 ml.min-1.g-1, infarct size reduced 46%) but not in dogs with more severe ischemia. Only R15.7 was effective in dogs with severe ischemia. Although MHM.23 and R15.7 produced similar inhibition of tissue PMN accumulation, as reflected by myeloperoxidase activity. R15.7 markedly inhibited H2O2 production by PMNs after exposure to platelet-activating factor, whereas MHM.23 had only a minimal effect. The effectiveness of different anti-CD18 MAb in preventing reperfusion injury appears to be 1) highly dependent on the specific anti-CD18 MAb employed, 2) predicted only partially by in vitro binding to PMNs, static in vitro tests of PMN adherence, or the extent of inhibition of PMN accumulation in vivo, 3) related more to their ability to inhibit oxidant release from activated PMNs, and 4) strongly influenced by the severity of myocardial ischemia before reperfusion.

Animals↗
PubMed1996

Serum tumor necrosis factor in mesangial IgA glomerulonephritis with macroscopic hematuria in children.

Tumor necrosis factor (TNF)-alpha and interferon (INF)-gamma levels were measured in the sera obtained from 29 patients with IgA glomerulonephritis (IgA GN), 8 patients with minimal change nephrotic syndrome (MCNS) and 12 patients with upper respiratory tract infection (URI) without renal diseases in children. The serum TNF-alpha level of IgA GN was 123.0 +/- 175.4 pg/ml, MCNS was 4.9 +/- 4.0 pg/ml and URI was 10.5 +/- 4.5 pg/ml respectively. The serum TNF-alpha level of IgA GN was significantly higher than those of MCNS and URI. The serum TNF-alpha level of URI was on the high trend compared with that of MCNS, but was not statistically significant. Although the TNF-alpha level was related to mesangial cell proliferation in patients with IgA GN, it was unrelated to the grade of mesangial matrix expansion and magnitude of proteinuria. In 17 patients with IgA GN having macroscopic hematuria, the serum TNF-alpha level was 190.5 +/- 201.6 pg/ml, and in other IgA GN patients with microscopic hematuria it was 37.4 +/- 75.7 pg/ml. The serum TNF-alpha level of IgA GN with macroscopic hematuria was significantly higher than that with microscopic hematuria. In 6 patients with IgA GN with macroscopic hematuria, the serum TNF-alpha level was significantly decreased after macroscopic hematuria disappeared. The mean serum IFN-gamma level of IgA GN was 0.3 +/- 0.6 IU/ml, and MCNS was not detectable. Although the serum IFN-gamma level was related to mesangial cell proliferation in patients with IgA GN, it was unrelated to magnitude of proteinuria, the grade of mesangial matrix expansion and also the presence or absence of macroscopic hematuria. We suggest that macroscopic hematuria of IgA GN was closely related to the serum TNF-alpha level.

Adolescent↗
PubMed1996

Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: Nitrates dilate coronary arteries, ameliorate myocardial ischemia, minimize left ventricular remodeling, and reduce mortality in patients with acute myocardial infarction. However, the effects of long-term treatment with nitrates on cardiac events in patients with healed myocardial infarction are not known. METHODS AND RESULTS: A total of 1,002 patients with healed myocardial infarction (789 male and 213 female) were randomly divided into 2 groups: treatment with nitrates or nontreatment. The mean observation period was 18.0 +/- 19.9 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics of the 2 groups were also compared to determine any effects on outcome. Among the 621 cases treated with nitrates, 41 cases (6.6%) experienced cardiac events during the observation period, whereas only 12 of the 381 cases that were not treated with nitrates (3.1%) had cardiac events. This difference was statistically significant (p < 0.05; odds ratio 2.17; 95% confidence interval 1.13-4.19). There were no differences in the incidence of noncardiac death or being lost to follow-up between the 2 groups. Although the precise mechanism of this increase in the occurrence of cardiac events by long-term treatment with nitrates is not clear, nitrate tolerance with possible rebound and neurohormonal effects may be involved. CONCLUSION: Long-term treatment with nitrates increased cardiac events in patients with healed myocardial infarction.

Aged↗
PubMed1996

Expression of the chitinase III gene of Aeromonas sp. no. 10S-24 in Escherichia coli.

The chitinase III gene of Aeromonas sp. No. 10S-24 was expressed in Escherichia coli. Production of chitinase III by E. coli was 3-fold higher than that of chitinases in the culture supernatant of Aeromonas sp. The enzyme from E. coli was purified and characterized. The molecular weight of the chitinase III from E. coli was estimated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) to be 55,000. This agreed with the calculated molecular weight of the mature chitinase III (54,111). However, it was different from that of the enzyme from Aeromonas sp. It showed that the chitinase III from Aeromonas sp. had an additional sugar chain, causing the higher molecular weight. Chitinase III from E. coli had almost the same enzymatic properties as chitinase III from Aeromonas sp., but the specific activity of the chitinase III from E. coli is slightly higher than that of the native chitinase III. Both enzymes hydrolyzed chitosan (80% deacetylated) well.

Aeromonas↗
PubMed1996

Structures and activity of cellulase inhibitors enzymatically synthesized from cellooligosaccharides and 1-deoxynojirimycin.

Cellulase inhibitors were synthesized from cellooligosaccharides and 1-deoxynojirimycin (DNJ) by transglycosylation, using a commercial cellulase. The structures of these cellulase inhibitors were proved to be 4-O-beta-cellobiosyl-DNJ, 4-O-beta-D-glucopyranosyl-DNJ and 6-O-beta-cellobiosyl-DNJ by the results of 13C- and 1H-NMR analyses. The inhibitory activity of each inhibitor was investigated against several carboxymethylcellulases.

1-Deoxynojirimycin↗
PubMed1996

Effect of eel ventricular natriuretic peptide on the kidney and cardiovascular system in the dog.

Ventricular natriuretic peptide (VNP), a possibly new type of natriuretic peptide with an extended C-terminal tail, has been isolated from eel cardiac ventricles. We investigated the effects of eel VNP on the kidney and cardiovascular system and compared these results with those of mammalian peptides in dogs. Eel VNP, human (dog) ANP, human and dog BNPs were infused into the renal artery at non-hypotensive doses. All peptides produced similar diuresis and natriuresis, but cardiac output and the left and right ventricular stroke work were decreased by BNPs, but ANP and eel VNP did not change these parameters. Systemic vascular resistance was increased by BNPs, but unaffected by other peptides. These results show that eel VNP has renal effects similar to ANP and BNP, but it elicits responses in the heart different from those of BNPs in anesthetized dogs.

Animals↗
PubMed1996

CBFB/MYH11 fusion transcripts in a case of acute myelogenous leukemia (M1) with partial deletion of the long arm of chromosome 16.

Pericentric inversion of chromosome 16 [inv(16)(p13q22)] is seen in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. This inversion juxtaposes the MYH11 gene on p13 and the CBFB gene on q22, resulting in the formation of a chimeric mRNA transcript. We describe a patient with acute myelogenous leukemia (M1), with del(16)(q22), who expressed the chimeric transcript. Reverse transcriptase polymerase chain reaction and the sequencing of its product showed fusion of 5'CBFB at position 495 to 3'MYH11 at position 1201. To our knowledge, this is the first report of an AML (M1) case with del(16) and CBFB/MYH11 rearrangement.

Amino Acid Sequence↗
PubMed1996

[A 10-year-old girl with anticardiolipin antibody, who showed bleeding tendency].

We described a 10-year-old girl with SLE complicated with anticardiolipin antibody, who showed bleeding tendency since infant. Her platelet was 6 x 10(3)/microliter. The APTT was remarkably prolonged. The platelet count was normalized after steroid treatment. A false positive Venereal Disease Research Laboratory (VDRL) test, lupus anticoagulants and anticardiolipin antibodies (IgG and IgM) were positive. Her symptoms and the laboratory data fulfilled the criteria of antiphospholipid syndrome. Renal biopsy was performed because of proteinuria, hematuria and the positive of anti-nuclear antibody. The pathology of kidney showed that of lupus nephritis (diffuse membranous glomerulonephritis), and she was diagnosed SLE. She showed no laboratory findings of hyperfibrinolysis and no symptoms of thrombosis under the steroid treatment for 3 years.

Antibodies, Anticardiolipin↗
PubMed1996

Studies on the reduction indices of the deciduous teeth of Chinese living in Taiwan.

The reduction index of deciduous teeth was investigated statistically. Materials used were plaster casts of the deciduous dentition taken from Chinese children living in Taiwan. The reduction indices showed no sexual differences. In the maxillary teeth, reduction indices of the bucco-lingual diameters (BL) had the largest values, followed by those of the mesio-distal diameters (MD), and those of the crown area (AREA) which were the least. In contrast to the maxillary teeth, in the mandibular teeth, the reduction indices of MD and those of BL had nearly the same values although the reduction indices of MD were slightly larger than those of BL in females (p < 0.05). With respect to the difference between the maxilla and the mandible, in deciduous incisors the reduction index of MD in the mandible was larger than that in the maxilla (p < 0.01). While in BL the reverse relation was noted. In the deciduous molars the reduction indices of BL and AREA in the maxilla were larger than those in the mandible (p < 0.01). The reduction indices showed no significant difference among the Mongoloid populations sampled. This result may be explained by the primitiveness of deciduous teeth.

Asian People↗
PubMed1996

Comparison of the crown dimensions between the maxillary second deciduous molar and the first permanent molar.

The morphologic relationship of the crown structures of the maxillary second deciduous molar (m2) and the first permanent molar (M1) was investigated with odontometric methods. Materials used were 124 male dental casts taken from Chinese living in Kaohsiung (Taiwan). The mesiodistal and buccolingual diameters, cusp sizes, and intercusp distances were measured. The mean crown diameters were larger in M1 than in m2. The tooth crown proportions were similar in m2 and M1. The intercusp distance was compressed buccolingually in m2. With respect to the relative cusp size, the paracone was not significantly different between m2 and M1. The metacone was relatively larger in m2 than M1, while lingual cusps (protocone and hypocone) were relatively smaller in m2 than in M1. Principal component analysis was performed to investigate factors influencing the variation in crown dimensions of the two teeth. Four components were extracted: (1) buccolingual intercusp distances, (2) crown proportion (mesiodistal and buccolingual diameters), (3) mesiobuccal and distolingual compression, and (4) protocone and mesiodistal intercusp distance. Analysis of principal component scores indicated that the crown proportions of m2 and M1 were similar. The m2 had a smaller protocone and more buccolingually compressed intercusp distances than did M1. The morphologic characteristics of the crown of m2 indicate that it is more primitive and has developed less than M1.

Humans↗
PubMed1996

Basophilic deposits on the cupula: preliminary findings describing the problems involved in studies regarding the incidence of basophilic deposits on the cupula.

In this study, the possibility of whether basophilic deposits adhered to the cupulas in the semicircular canals was investigated histologically. Results indicated that basophilic deposits were present in all three cupulas of the semicircular canals. The overall incidence of basophilic deposits in the superior, lateral and posterior semicircular canal cupulas was 26%, 41% and 37%, respectively. The incidence of basophilic deposits bound to the cupulas increased with age. The possible origin of these basophilic deposits on the cupulas and the increased incidence of basophilic deposits with increasing age are discussed.

Adult↗
PubMed1996

Influence of vestibular organ stimulation on stomach movement and respiration.

Some previous investigators have reported controversial results in the stomach movement in response to labyrinthine stimulation (1). The purpose of the present study was to investigate the influence of vestibular stimulation on the stomach movement and respiration in anesthetized cats, and to investigate the differences between increased and decreased responses of the stomach movement. This study used an electrophysiological technique: a bipolar stainless-steel stimulating electrode with a tip diameter of 20 microns introduced chronically into the anterior and/or lateral semicircular canal (2). The intragastric pressure was recorded by using a balloon-transducer system. Respiration was recorded by measurement of the thorax. When the peripheral labyrinth was stimulated, we found conflicting results in that the pressure in the stomach increased several times and sometimes decreased. Respiration usually became irregular or intensified. It seems that forced respiration may be involved in vestibular vomiting but we were unable to induce vomiting.

Animals↗