Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 271 records · Page 15Linked to original sources

PubMed1999

Structural features in heparin that interact with VEGF165 and modulate its biological activity.

The 165 amino acid form of vascular endothelial growth factor (VEGF165) is a heparin-binding growth factor with mitogenic activity for vascular endothelial cells. We examined activities of various heparin derivatives toward their interactions with VEGF165 using an enzyme-linked immunosorbent assay and elucidated the structural features in heparin for the interactions. Native heparin interacted with VEGF165, whereas N-desulfated, N-acetylated (N-DS, N-Ac-) heparin, and 6-O-desulfated (6-O-DS-) heparin did not. The 2-O-desulfated (2-O-DS-) heparin retained the ability for the interaction with VEGF165. In contrast, the 2-O-DS-heparin exhibited no ability for the interaction with FGF-2 and HGF. Thus, structural requirements in heparin for the specific interaction with VEGF165 are distinct from those with FGF-2 and HGF which require a high content of 2-O-sulfate groups. In a cell proliferation assay, native heparin and 2-O-DS-heparin exhibited inhibitory abilities for VEGF165-induced proliferation of human umbilical vein endothelial cells (HUVECs) with their high concentrations (more than 64 microg/ml), while only native heparin could enhance the proliferation of the chlorate-treated cells. These results suggested that a high content of 2-O-sulfate groups is not required for the specific interaction with VEGF165alone, although it is essential for the mitogenic activity of the growth factor.

Binding Sites↗

PubMed1999

Influence of the male reproductive tract on the reproductive potential of round spermatids abnormally released from the seminiferous epithelium.

Round spermatids can be collected from testicular biopsy material or occasionally from semen samples. We evaluated the influence of the passage of round spermatids through the male reproductive tract on their reproductive potential. A model of abnormal release of round spermatids from the seminiferous epithelium was created in mature male rats (group A). Additional sham-treated rats of the same age served as a control group (group B). Round spermatids were collected from the testicles of rats of both groups, the epididymides of rats of group A, and the vaginae of mature female rats mated with rats of group A. Isolated round spermatids were processed for ooplasmic injections. Injected oocytes were cultured. At 96 h post-injection, the blastocyst development rate was significantly higher in the groups of oocytes injected with testicular spermatids than the groups of oocytes injected with spermatids recovered from the vaginae, or the head, body, or tail of the epididymides. It appears that round spermatids recovered from testicular biopsy material have larger reproductive capacity than ejaculated round spermatids, due to mechanical or chemical detrimental influences of storage/passage through the male reproductive tract (outside the testicle) on the capacity of round spermatids to induce optimal early embryonic development.

Animals↗

PubMed1999

Molecular cloning and expression analysis of a gene for a sucrose transporter in maize (Zea mays L.).

Here we report the cloning of a sucrose transporter cDNA from maize (Zea mays L.) and an analysis of the expression of the gene. A cDNA clone (ZmSUT1) was identified as a sucrose transporter cDNA from its sequence homology at the amino acid level to sucrose transporters that have been cloned from other higher plant species. Based on the results of genomic Southern hybridization, ZmSUT1 appears to be a single copy gene. A Northern blot analysis of seedlings and leaf blades suggests that the sucrose transporter is involved in the export of accumulated carbohydrates from source leaf blades. From the measurements of transcript levels and carbohydrate contents in mature leaf blades, we propose that the expression of the gene for the maize sucrose transporter is positively regulated by the amounts of soluble sugars such as sucrose and glucose in source leaves of maize. In addition, based on the tissue specificity of the expression of the gene in maize plants at the reproductive stage, it is possible that the sucrose transporter acts in sink tissues such as pedicles as well as in source tissues such as leaf blades.

Biological Transport↗

PubMed1999

Effects of OK-432 on the proliferation and cytotoxicity of lymphokine-activated killer (LAK) cells.

We studied the effect of a streptococcal preparation, OK-432, on the cytotoxicity and the proliferation of lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy. Peripheral blood mononuclear cells (PBMC) were derived from healthy donors and patients with malignant brain tumors. We divided PBMC into two groups; these cells then were stimulated with interleukin-2 in the presence or absence of OK-432. OK-432 was added only in the initial 3 days during the 3-week midterm culture period. Then, we compared OK-432-stimulated LAK (OK-LAK) cells with standard LAK (sLAK) cells in terms of their rate of proliferation and cytotoxicity. OK-LAK cells proliferated more rapidly than sLAK cells. The cytotoxicity of OK-LAK cells increased, whereas that of sLAK cells decreased. We also investigated the phenotypic differences between these two types of LAK cells and found that, on day 21, the OK-LAK cells consisted mostly of CD3-CD56+ NK cells, whereas the sLAK cells consisted mostly of CD3+CD56- T cells. The difference in their level of cytotoxic potential might be explained by the difference of predominant phenotype.

Antigens, CD↗

PubMed1999

Pathology of ossification of the posterior longitudinal ligament and ligamentum flavum.

Ossification takes place in the posterior longitudinal ligament and ligamentum flavum of the spine under certain conditions of unknown nature. Ossification of these ligaments has the following characteristics: (1) ectopic bone formation occurring within the spinal ligaments; (2) ossification accompanies ligamentous tissue hyperplasia and cell proliferation; (3) before ossification, fibrocartilaginous cell proliferation, calcification and tissue resorption with vascular ingrowth take place sequentially; (4) ossification of the ligament has a specific site of predilection and often occurs in combination with senile ankylosing vertebral hyperostosis (Forestier's disease) or diffuse idiopathic skeletal hyperostosis; and (5) ossification and symptom development are remarkably more frequent in the Japanese population. Recent studies revealed that bone morphogenetic proteins and transforming growth factor-beta played an important role in the matrix hyperplasia and ossification of the spinal ligament, and metabolic and genetic aberration often characterized patients suffering from this disorder.

Humans↗

PubMed1999

Quantitative EEG analyses and surgical outcome after corpus callosotomy.

PURPOSE: To clarify the relation between quantitative electroencephalogram (EEG) findings and outcome following corpus callosotomy (CC). METHODS: The degree of bilateral synchrony and morphologic similarity of spike-wave discharges was analyzed by using a cross-correlation analysis and the measurements of amplitude differences between bilateral homologous regions in 22 patients who underwent anterior CCs for intractable symptomatic generalized epilepsies (SGE; 17 patients) and frontal lobe epilepsy (five patients). RESULTS: Interictal generalized synchronous spike-wave (GSSW) bursts in the SGE patients were disrupted and changed to unilateral spike-waves (USWs) in 11 patients and to bilaterally independent spike-waves (BISWs) in six. The USW group had better surgical outcome than the BISW group. Preoperatively, the USW group had significantly lower interhemispheric synchrony (IS) and fewer regional changes in the side leading in time and the side dominant for amplitude, suggesting unilaterally predominant epileptogenesis that triggered the secondary bilateral synchrony. Postoperatively, the BISW group had a more marked reduction in IS because of independent discharges from bilateral epileptogenic areas, and the USW group had a greater amplitude difference because of unilateralized spike-waves. In addition, an excellent surgical outcome was related to (a) the preoperative degree of the morphologic similarity of the bilateral spike-waves (only a small variation during a burst of spike-waves) and the few instances of regional changes in the side leading in time and in the side dominant for amplitude; and (b) to large postoperative amplitude differences. CONCLUSION: Preoperative quantitative EEG analyses enabled us to predict the underlying conditions of epileptogenesis and the surgical outcomes in patients undergoing CC.

Adolescent↗

PubMed1999

Mechanical stress-induced Ca2+ entry and Cl- current in cultured human aortic endothelial cells.

A fluid stream through a microtube was applied to cultured human aortic endothelial cells to investigate the endothelial responses of both the ionic currents and intracellular Ca2+ concentration ([Ca2+]i) to mechanical stimulation. The fluid stream induced an increase in [Ca2+]i that was dependent on both the flow rate and the extracellular Ca2+ concentration. Gd3+ and niflumic acid inhibited the fluid stream-induced increase in [Ca2+]i, whereas Ba2+ and tetraethylammonium ion exhibited no effect. The fluid stream-induced [Ca2+]i increase was accompanied by the activation of an inward current at -52.8 mV. The reversal potential of the fluid stream-induced current shifted to positive potentials when the external Cl- concentration was reduced but was not affected by variation of the external Na+ concentration. During the exposure to the fluid stream, [Ca2+]i was voltage dependent, i.e., depolarization decreased [Ca2+]i. We therefore conclude that the fluid stream-induced current is largely carried by Cl- and that the Cl- current may thus play a role in modulating the Ca2+ influx by altering the membrane potential of endothelial cells.

Aorta↗

PubMed1999

Leopard syndrome associated with hyperelastic skin: analysis of collagen metabolism in cultured skin fibroblasts.

We present a patient with Leopard syndrome and hyperelastic skin. Biochemical analysis using cultured skin fibroblasts showed normal type III and V collagen synthesis, lysyl hydroxylation level of type I procollagen and processing of pro-alpha(1) and alpha(2)(I). Our results suggest that molecular defects of hyperelasticity in Leopard syndrome are not related to abnormal collagen metabolism, although not all steps of collagen synthesis have been investigated.

Abnormalities, Multiple↗

PubMed1999

Histamine H2 receptor antagonism by T-593: studies on cAMP generation in Hepa cells expressing histamine H2 receptor.

Histamine H2 receptor antagonism by T-593 was investigated in Hepa cells expressing canine histamine H2 receptors. T-593 inhibited generation of cAMP in Hepa cells stimulated by 10(-5) mol/l histamine with an IC50 value of 2.3 x 10(-6) mol/l, (S)-(-)-T-593, one of the enantiomers comprising racemic T-593, inhibited cAMP generation with an IC50 value of 6.1 x 10(-7) mol/l. On the other hand, the other enantiomer (R)-(+)-T-593 exhibited only a negligible effect. Incubation of the cell with (S)-(-)-T-593 for 60 min depressed the maximal response of the concentration-response curve of histamine with a nonparallel rightward shift. The slope of a Schild plot was 1.27. In contrast, (S)-(-)-T-593 caused a parallel rightward shift of the curve, with a Schild plot slope that did not significantly differ from unity, by treating the cells for 15 min. The H2 receptor-blocking action of (S)-(-)-T-593 remained almost unaffected after washing out the drug, whereas the effect of ranitidine was reversible after washing. These results suggest that T-593 possesses a time-dependent insurmountable antagonistic action against histamine H2 receptor. T-593 may interact with the histamine H2 receptor molecule in a slowly associable and dissociable manner.

Animals↗

PubMed1999

High Toxoplasma seroprevalence associated with meat eating habits of locals in Nepal.

A serosurvey of Toxoplasma gondii infection in apparently healthy subjects (n = 404) living in Achham (n = 215) and Dang (n = 189) districts in western Nepal was carried out. An interview with 249 participants, each representing a household, was also conducted. This interview pertained to their meat eating habits and the keeping of cats in their houses. Toxoplasma antibodies were detected by using the microlatex agglutination test. The overall seroprevalence was 65.3% with no significant difference in the two districts (Achham: 66.9% and Dang: 63.5%) included (p = 0.546). Females and the Indo-Aryan ethnic-group showed marginally higher prevalence compared with their male (p = 0.545) and Tibeto-Burman (p = 0.075) counterparts. The majority of the infections was found to have occurred during childhood. The frequency of meat eating in western and eastern regions differed greatly (p = 0.000) with the people in the eastern region being frequent meat eaters than those in the western region. About one-third of the subjects, all Indo-Aryans, in the western region had the raw meat eating habit but none in the eastern region. Approximately 7.0% of households in both western and eastern regions kept cats. The present findings demonstrated a typical role of meat eating habits of people in the high Toxoplasma seroprevalence in Nepal.

Adolescent↗

PubMed1999

Apical hypertrophic cardiomyopathy and hepatitis C virus infection.

The familial form of hypertrophic cardiomyopathy (HCM) is attributed to mutations in the genes for contractile proteins, but the etiology of non-familial form remains unknown. This study was designed to examine the clinical features, histopathologic changes, and hepatitis C virus (HCV) genomes in patients with HCM associated with HCV infection. Anti-HCV antibody was present in the sera of 9 of 65 patients (13.8%) with HCM versus 2.41% in a control population of voluntary blood donors in Japan, a statistically significant difference (p<0.0001). Among these 9 patients, 6 had ace-of-spades-shaped deformities of the left ventricle with apical hypertrophy. Myocardial fibrosis was found in all patients, and mild cellular infiltration was observed in 5 patients. Type 1b HCV RNA was present in the sera of 5 of the 9 patients. The copy number of HCV was 5.5x10(3)-8.6x10(5) genomes/ml serum, and multiple clones of HCV were detected in the sera of each patient by an analysis of the hypervariable regions using fluorescent single-strand conformation polymorphism. Positive strands of HCV were found in the hearts of 5 patients, and negative strands in the hearts of 2 patients. A high prevalence of HCV infection was found in patients with HCM, particularly of the apical variety, suggesting that HCV is an important causal agent in the pathogenesis of the disease.

Adolescent↗

PubMed1999

Cytokine gene expression during the development of graft coronary artery disease in mice.

Immunologic injury to heart allografts is an initial and essential event in the pathogenesis of graft coronary artery disease (GAD). A variety of cytokines expressed in heart allografts modify both acute rejection and chronic inflammation, and could contribute to the development of GAD. The present study investigated the gene expression of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and Fas ligand in chronically rejecting DBA/2-to-B 10.D2 mouse heart allografts at defined intervals of 7, 14, 28, or 70 days after transplantation by semiquantitative reverse transcriptase-polymerase chain reaction. GAD developed gradually, showing the highest value for mean intima/media ratio at day 70. Fas ligand, and the Th1 cytokines IL-2 and IFN-gamma, were vigorously induced in allografts at day 7, when histology showed pronounced parenchymal rejection, and rapidly decreased by day 28. However, the level of mRNA expression of Th2 cytokines, IL-6 and IL-10, and other inflammatory cytokines, TNF-alpha and IL-1beta, were still elevated on day 28. The persistent expression of specific cytokines suggests an important role in chronic inflammation. Thus, a persistently high level expression of inflammatory cytokines could be associated with chronic inflammation in the allografts, which promotes the development of GAD.

Animals↗

PubMed1999

High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity.

Results of recent studies suggest that proinflammatory cytokines cause myocardial contractile dysfunction, and that the drugs used to treat heart failure modulate the production of cytokines. This study was designed to examine the effects of digoxin in a murine model of heart failure induced by viral myocarditis. Four-week-old inbred DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis virus (EMCV). Digoxin was given orally in doses of 0.1, 1 or 10 mg/kg daily from the day of virus inoculation. Interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha production in the heart were measured on day 5 after EMCV inoculation by enzyme-linked immunosorbent assay. The 14-day mortality tended to be increased in mice treated with 1 mg/kg, and was significantly increased in the group treated with 10 mg/kg per day. Myocardial necrosis and cellular infiltration on day 6 were significantly more severe in the high-dose digoxin group than in the control group. In the animals treated with 1 mg/kg digoxin, IL-1beta was significantly higher than in the control group. Intracardiac TNF-alpha levels were increased in a dose-dependent manner. These results suggest that digoxin worsens viral myocarditis, and that its use in high doses should be avoided in patients suffering from heart failure due to viral myocarditis.

Animals↗

PubMed1999

Utilization of intestinal triglyceride-rich lipoproteins in mammary gland of cows.

Elution profiles of total lipoproteins, apolipoprotein B (apoB) concentrations in lipoproteins, and plasma triglyceride (TG) levels were examined in early-, late-, and non-lactating cows. Additionally, arteriovenous (A-V) differences were also measured to elucidate the uptake of TG and apoB-containing lipoproteins in mammary gland. Non-lactating cows showed three major peaks corresponding to triglyceride-rich lipoprotein (TRL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fraction, whereas both early- and late-lactating cows revealed two peaks corresponding to TRL and HDL. The peak area of TRL in early- and late-lactating cows were significantly (p < 0.05) smaller than that in non-lactating cows. The plasma TG levels and apoB-48 concentrations of TRL in early- and late-lactating cows were also significantly (p < 0.01) lower. Furthermore, early lactating cows showed significantly (p < 0.05) larger A-V differences in both plasma TG and apoB-48 concentration of TRL than those in late- and non-lactating cows. These results suggested that TG in exogenous (intestinal) TRL was utilized for milk fat synthesis in lactating mammary gland of cows by the receptor-mediated uptake.

Animals↗

PubMed1999

Prevalence and persistence of Salmonella in broiler chicken flocks.

Cecal contents of 2,345 broiler chickens consisting of 28 flocks originated from 12 farms were examined for the prevalence of Salmonella to know the actual status of infection with Salmonella in the chicken flocks. Salmonella was isolated from 336 (14.3%) samples. From these isolates, eight serovars were identified. Of the 336 Salmonella isolates, 242 (72.0%) were serotyped as S. Blockley, 60 (17.9%) S. Hadar, 15 (4.5%) S. Bredeney, nine (2.7%) S. Schwarzengrund, four (1.2%) S. Anatum, three (0.9%) S. Enteritidis, two (0.6%) S. Ohio, and one (0.3%) S. Livingstone. The same serovars of Salmonella were repeatedly found in the chickens from the same farms. S. Typhimurium and S. Enteritidis were detected in pooled broken eggshell samples collected from the hatchery. Analysis of plasmid profiles revealed 11 patterns of S. Blockley and seven patterns of S. Hadar. Strains of the same plasmid profiles of S. Blockley were isolated repeatedly from the same farm over one year after the first isolation.

Animals↗

PubMed1999

Relationship between exercise capacity and ventilatory equivalent for carbon dioxide in patients with stable old myocardial infarction.

The aim of the present study was to evaluate the relationship between exercise capacity and ventilatory response in patients with stable old myocardial infarction. We performed cardiopulmonary exercise test in 61 patients with stable old myocardial infarction and in 30 healthy men. Each subject exercised on a bicycle ergometer until exhaustion. Patients who had anginal pain or electrocardiographic ischemic changes during exercise were excluded. The patients were classified into three groups according to peakVO2 achieved during exercise, using Weber's method: group A, peakVO2 > or = 21 ml/min/kg (n = 4); group B, 14 < or = peakVO2 < 21 ml/min/kg (n = 45); and group C, peakVO2 < 14 ml/min/kg (n = 12). With progressive increases in VCO2, VE increased linearly below the anaerobic threshold (AT) level. The slope of the linear regression line between VCO2 and VE (SLOPE) was calculated in each subject. The mean SLOPE of the healthy men (group N) and groups A, B and C were 25.8 +/- 0.5, 25.1 +/- 0.5, 28.9 +/- 0.8 and 37.1 +/- 1.7 (x 10(-3), respectively. Thus, the SLOPE was steeper in patients with lower peakVO2. It is difficult to perform a maximal exercise tolerance test on patients with chronic heart failure to evaluate their exercise capacity. We can assess exercise capacity by the slope of the linear regression line between VCO2 and VE (SLOPE) at the lower exercise level.

Aged↗

PubMed1999

Emesis in the shrew mouse (Suncus murinus) induced by peroral and intraperitoneal administration of staphylococcal enterotoxin A.

Peroral and intraperitoneal administration of staphylococcal enterotoxin A (SEA) to Suncus murinus elicited an emetic response. The 50% emetic dose of SEA by peroral administration was found to be 32 microg per kg of body weight, whereas that by intraperitoneal administration was 3 microg per kg. Multiple emetic responses occurred 70 to 108 min after peroral administration of an emetic dose of SEA. Similar responses occurred 65 to 102 min after intraperitoneal injection of an emetic dose of SEA. No significant difference in vomiting was observed between male and female animals. Anti-SEA serum neutralized SEA-induced emesis in S. murinus. These findings indicate that S. murinus may serve as a suitable animal model to study the enterotoxigenicity of SEA.

Administration, Oral↗

PubMed1999

Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.

MCAF (monocyte chemotactic and activating factor)/MCP-1 (monocyte chemoattractant protein-1) is an important mediator of monocyte recruitment to inflammatory sites. However, its pathophysiologic role in myocardial reperfusion injury remains unknown. Male Wistar rats were anesthetized, and the left anterior descending coronary artery was ligated for an hour, after which the ligature was released. Northern blotting analysis revealed that MCAF/MCP-1 mRNA expression increased 16-fold in the reperfused region at 12 hours after reperfusion. MCAF/MCP-1 concentration in plasma and the heart was already elevated after hour of ischemia in this model. Goat polyclonal antibodies were prepared by repeated immunization of animals with purified, recombinant rat MCAF/MCP-1, and the neutralizing activities of this antibody were confirmed by monocyte chemotaxis assay and administration to rats with crescentic glomerulonephritis. Intravenous injection of anti-MCAF/MCP-1 antibody significantly reduced the infarct size at 24 hours after reperfusion compared with the injection of control IgG (33.9 +/- 5.1% vs 49.4 +/- 2.7% of ischemic area, mean +/- SEM). Administration of this antibody markedly decreased the intercellular adhesion molecule-1 mRNA expression and infiltration of macrophages, which suggested the pathophysiologic role of MCAF/MCP-1. Neutralization of MCAF/MCP-1 is beneficial by preventing reperfusion injury in a rat model of myocardial ischemia and reperfusion.

Animals↗