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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 91 records · Page 5Linked to original sources
PubMed1999

Protective effects of intranasal vaccination with plasmid encoding pseudorabies virus glycoprotein B in mice.

Intranasal administration of plasmid DNA encoding glycoprotein B of pseudorabies virus into mice induced both serum and secretory antibody responses. These mice resisted intranasal challenge with lethal dose of the virus, but did not intraperitoneal challenge. On the other hand, intramuscular injection of the plasmid induced less secretory and higher serum antibody responses than those of intranasally vaccinated mice. None of them was protected from virus challenge. The present results suggest that administration of plasmid DNA encoding glycoprotein B by respiratory mucosal route generates local secretory antibodies which serve to protect animals from pseudorabies virus infection.

Administration, Intranasal↗
PubMed1998

Characterization of avian H5N1 influenza viruses from poultry in Hong Kong.

The transmission of avian H5N1 influenza viruses to 18 humans in Hong Kong in 1997 with six deaths established that avian influenza viruses can transmit to and cause lethal infection in humans. This report characterizes the antigenic and biological properties of the H5N1 influenza viruses isolated from chickens, ducks, and geese from farms and poultry markets in Hong Kong during 1997 and compares them with those of virus isolated from the index human case. Each of the H5N1 viruses from Hong Kong poultry markets that were tested were lethal in chickens, possessed polybasic amino acids at the carboxy-terminus of HA1, and by definition were highly pathogenic in poultry. The available nonpathogenic H5 influenza viruses and the pathogenic H5N1 virus from Hong Kong were analyzed with monoclonal antibodies prepared to A/chicken/Pennsylvania/1370/83 (H5N2). The analysis revealed limited antigenic drift in 15 years and established that monoclonal antibodies are useful reagents for identification and antigenic analysis of avian strains that may transmit to humans in the future. One of the monoclonal antibodies permitted separation of the H5N1 influenza viruses from poultry into two groups that correlated with the presence or absence of a carbohydrate at residue 158 adjacent to the receptor binding site on HA. The H5N1 viruses examined replicated in geese, pigs, rats, and mice, but to only a very limited extent in ducks. It is noteworthy that all infected geese shed virus and that the H5N1 viruses caused disease signs and death in a portion (3 of 16) of the geese, with evidence of systemic spread to the brain. The tropism for geese is unusual and may provide insight into the origin of these viruses. In mice, the H5N1 virus caused lethal pneumonia and spread systemically to the brain. Mice would thus provide an ideal model system for studying immune responses and pathogenesis. Transmission experiments in chickens revealed that the H5N1 viruses are spread by fecal-oral transmission rather than by aerosol, and that the viruses are inactivated by drying of feces at ambient temperature. However, infectivity is maintained for at least 4 days in wet feces at 25 degreesC. There were differences in the morphology of the H5N1 viruses isolated from birds and humans. The perpetuation of H5N1 influenza viruses in the poultry markets in Hong Kong and the transmission of these viruses to humans emphasize the importance of these markets in the epidemiology of influenza. The poultry markets are of critical importance in the perpetuation and transmission of influenza viruses to other avian species and to mammals, including humans.

Animals↗
PubMed1998

Cancer cells overexpress mRNA of urokinase-type plasminogen activator, its receptor and inhibitors in human non-small-cell lung cancer tissue: analysis by Northern blotting and in situ hybridization.

The transcriptional localizations of urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitors (PAI-1 and PAI-2), which are possibly involved in cancer metastasis, have not been determined in human lung cancer. To identify their regulation in primary non-small-cell lung cancer, we assayed mRNA levels by Northern blot analysis in 25 cases and determined the localizations of mRNA by in situ hybridization in 10 cases. The amounts of uPA and PAI-2 mRNA were significantly higher in cancerous relative to normal lung tissues. However, no significant difference was observed in uPAR and PAI-1 mRNA levels. All transcripts were present in cancer cells and were predominantly located in tumor edges in several cases. In addition, PAI-1 transcripts were more abundant in poorly and moderately differentiated carcinomas relative to well-differentiated carcinomas and PAI-2 transcripts were more abundant in squamous cell carcinomas than in adenocarcinomas. Thus, PAIs may be involved in modulation of malignant potency. Our results indicate that human non-small-cell lung cancer cells can autonomously express the mRNAs of uPA, uPAR and PAIs, which are possibly involved in metastasis.

Adenocarcinoma↗
PubMed1998

A potent 5-hydroxytryptamine receptor (5-HT2A) antagonist, DV-7028, delays arterial thrombosis development in rats.

In our study, we demonstrated that DV-7028: (3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6, 7,8,9-tetrahydro-2H-pyrido [1,2,-a]-1,3,5-triazine-2, 4(3H)-dione maleate)--a selective 5-HT2A receptor antagonist, inhibited thrombus formation in the arterial thrombosis model and was completely ineffective in the prevention of venous thrombosis in the rat. In washed platelets prelabelled with 3H-serotonin, DV-7028 inhibited, in a dose-dependent manner, the collagen-induced secretion of serotonin. However, the uptake of serotonin into platelets was not affected by this substance. Administration of DV-7028 also inhibited platelet aggregation in the whole blood and platelet-rich plasma (PRP) induced by collagen, and diminished serotonin-induced aggregation of rat platelets in the presence of a sensitizing but nonaggregating amount of ADP, whereas it did not modify aggregation in PRP when induced by ADP. DV-7028 caused a concentration-dependent, almost parallel shift to the right of the concentration-response to serotonin for its pressor effect in the rat perfused tail artery. The present data demonstrate that DV-7028 exhibits 5-HT2A receptor antagonistic properties in the rat cardiovascular system, exhibits antithrombotic effect in the model of arterial but not venous thrombosis in rats. These results constitute further evidence of the possible importance of serotonin as a mediator of platelet thrombosis in arteries. Moreover, they can provide a useful tool for the prevention of various thrombotic diseases.

Animals↗
PubMed1998

Proteolysis of highly polysialylated NCAM by the tissue plasminogen activator-plasmin system in rats.

Tissue-type plasminogen activator (tPA), a serine protease which converts the zymogen plasminogen to the active protease plasmin, is believed to regulate neurite extension and neural cell migration by modulating extracellular metabolism. The highly polysialylated form of the neural cell adhesion molecule (NCAM-H) is strongly expressed in the developing brain and is believed to play a role in organizing the neural network. In this report, we incubated neonatal rat brain homogenates with human tPA and rat plasminogen in order to determine whether NCAM-H would be degraded. NCAM-H was degraded by plasmin which was formed from rat plasminogen by human tPA. The degradation was inhibited by the addition of plasminogen activator inhibitor type 1 (PAI-1) or aprotinin. These results suggest a possible contribution of the tPA-plasmin system to NCAM-H turnover in the developing brain.

Aging↗
PubMed1998

Effects of electric footshock and water immersion restraint stresses on fibrinolytic parameters in the plasma of rats.

Wistar rats were exposed to electric footshock (ES) or water immersion restraint stress (WS). Blood was taken immediately after, 24, or 48 hours after the stress. The stomachs of rats taken 1 hour after stress application indicate that there were many bleeding spots in the stomachs of WS rats, but practically no visible bleeding spots in the stomachs of ES rats. Plasma levels of t-PA antigens increased in ES rats up to 24 hours after the stress, but the t-PA antigen levels decreased up to 48 hours in ES rats. There were no changes in t-PA activities in plasma of WS rats, but the levels in ES rats decreased immediately and 48 hours after the stress. PAI activity did not change immediately after WS but increased 24 hours after the stress. There was no change in PAI activity in ES rats up to 48 hours. ELT did not change in ES rats, but prolonged in WS rats at 24 hours after the stress. There were significant negative correlations between t-PA antigen levels or activities and ELT in control rats. No correlation was observed in ES or WS rats between t-PA antigen levels and ELT, and no correlation was shown in WS rats between t-PA activities and ELT. Plasma levels of catecholamines increased at the 20-minute period during ES, which may not explain the delayed effects of ES on hemostatic balance. Plasma levels of arginine vasopressin increased significantly immediately after the shock up to 2 hours, indicating that the stress was conveyed to the hypothalamus during the stress application. These results may indicate that some stressors induce an increase or decrease in the local balance of fibrinolytic activities, resulting in bleeding or thrombosis in the local vessels. Such changes may not be detected in the general circulation due to the neutralization of locally induced fibrinolytic changes or the involvement of other hepatically originated hemostatic factors induced by stressors.

Animals↗
PubMed1998

Progressive expansion of hypertensive intracerebral hemorrhage by coagulopathy.

To test the hypothesis that an impaired coagulation system facilitates rapid expansion of hypertensive intracerebral hemorrhage (HICH), coagulation markers were assayed in plasma and their relations to both the hemorrhage size and its progressive expansion were analyzed. Ninety patients with HICH were studied. On admission, plasma samples were taken for the coagulation assay. Hematoma volume was calculated from a computed tomography (CT) scan and its enlargement was estimated by comparison to the volume of the hematoma calculated from a second CT scan taken later within 24 hr. Nine out of 90 patients showed enlargement in their hematoma size (enlarged hematoma group). Four of the enlarged hematoma group fell into acute fatal deterioration and died. Plasma levels of both fibrino peptide A (17.2+/-7.8 vs. 4.0+/-0.6 ng/ml, P < 0.05) and thrombin-antithrombin complex (21.9+/-3.1 vs. 7.4+/-2.8 ng/ml, not significant) were higher in the unchanged group than those in the enlarged hematoma group. In the hematoma-enlarged group fibrino-peptide A level did not exceed 10 ng/ml. In the hematoma unchanged group thrombin-AT-III complex values were positively correlated to hematoma volume. Thus, the coagulation system seemed to be highly activated depending on the hemorrhage volume within three hr after ictus in hypertensive intracerebral hemorrhage patients. When thrombin generation was not sufficient after bleeding, the hematoma seemed to be progressively enlarged. In conclusion, plasma levels of the coagulation markers on admission could be useful predictors of the possible enlargement of hematoma which leads to a poor outcome.

Aged↗
PubMed1998

Nicotine increases stress-induced serotonin release by stimulating nicotinic acetylcholine receptor in rat striatum.

We used a microdialysis technique to analyze the effects of footshock stress on the release of serotonin (5-hydroxytryptamine: 5-HT) in the striatum or prefrontal cortex (PFC) in rats that were pretreated with nicotine. Neither nicotine administration alone nor stress application alone changed 5-HT release. During stress application, however, both chronic nicotine administration and local infusion of nicotine to the striatum significantly increased 5-HT release in the striatum, though not in the PFC. These increases in 5-HT release were eradicated by a local infusion of mecamylamine. Release of 5-HT increased in the striatum during stress application when nicotine was injected to the striatum, while nicotinic injection to the dorsal raphe nucleus did not increase 5-HT release in the striatum. The present study demonstrates that nicotine induced a release of 5-HT upon stress application by stimulating presynaptic nicotinic receptors in the striatum.

Animals↗
PubMed1998

An attenuation mechanism of Newcastle disease vaccine strain TCND.

To provide information on the mechanism of attenuation of a Newcastle disease vaccine strain, TCND, we compared it with the parental virulent strain California 11,914 (CAL) biologically and genetically. It was found that TCND bore the fusion protein of virulent type, consisting of a pair of dibasic amino acid residues at the cleavage site and was a temperature sensitive (ts) mutant restricted to grow at 41.5 degrees C. Revertants were obtained by prolonged incubation of chicken embryos inoculated with TCND at the nonpermissive temperature. In cultured cells, viral gene transcription and protein synthesis of TCND occurred similarly to those of CAL and the revertants at 41.5 degrees C. Hemadsorption and immunofluorescence assays revealed that cell surface expression of functional hemagglutinin-neuraminidase (HN) of TCND at 41.5 degrees C was lower than that at 35 degrees C. The revertants exhibited lower activity in fusion assay than CAL and recovered virulence to chicken only in part. The results indicate that the ts mutation of TCND in association with the defect of HN glycoprotein transport is a mechanism of the attenuation, and in addition, some other factors such as fusion activity should be involved in the loss of virulence of CAL to chickens.

Amino Acid Sequence↗
PubMed1998

Remnant-like particle cholesterol is a major risk factor for myocardial infarction in vasospastic angina with nearly normal coronary artery.

We investigated the association of remnant-like particle cholesterol (RLP-C), with vasospastic angina (VSA). We selected 66 subjects with nearly normal coronary artery as a control group, and 74 VSA with nearly normal coronary artery, of whom 19 had prior myocardial infarction (MI). Coronary risk factors, triglyceride, lipoproteins and apolipoproteins were evaluated using stepwise discriminant analysis, smoking was the only discriminator of the control group from VSA and RLP-C was the only discriminator of VSA with MI from VSA without MI. In comparison between VSA with and without MI, using stepwise logistic regression analysis, the only significant variable was RLP-C, and odds ratio of RLP-C for MI was 1.59. Thus, RLP-C is a major discriminator of VSA with MI and appears to be a major risk factor for MI in VSA.

Adult↗
PubMed1998

SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset pure cerebellar ataxia.

Spinocerebellar ataxia type 6 (SCA6) is caused by small CAG repeat expansion in the gene encoding the alpha1A-voltage-dependent-calcium channel subunit (CACNLIA4) on chromosome 19p13, and is a subgroup of the late-onset pure cerebellar ataxia (ADCA III). To investigate the prevalence of SCA6 in the Japanese, we analyzed this mutation in 23 families and 12 probands with ADCA III. The specificity and stability of the CAG repeat were examined in additional individuals and families with other miscellaneous dominant SCAs. The CAG expansion of SCA6 gene was exclusively observed in 12 of 23 families (52%) and 12 proband cases with ADCA III, but not in others. The CAG repeat was 21-33 in the disease-associated alleles (n=56), and 4-18 in normal alleles (n=1148). Expanded alleles were stable during transmission, and a significant inverse correlation for CAG repeat number with age at onset was noted. Our results indicate that SCA6 shares approximately half of the ADCA III in the Japanese, and that gene mutations causing the remaining, have yet to be identified.

Adult↗
PubMed1998

Extracellular serotonin in the striatum increased after immobilization stress only in the nighttime.

The release of serotonin (5-HT) in the striatum and the motor activity of rats given the immobilization stress were measured using in vivo microdialysis techniques and locomotion counts. Serotonin release in the striatum did not change in the daytime and nighttime, but motor activity in the nighttime was significantly higher than in the daytime. Serotonin release was not significantly increased during immobilization stress in the daytime or nighttime. In the nighttime, however, after the end of stress, 5-HT release was significantly increased from 0.002 ng/dialysate to 0.47 ng/dialysate. The motor activities were also significantly increased after the stress in the nighttime. These results suggest that the effects of immobilization stress on serotonin release in the striatum were different in the daytime and nighttime. In the nighttime, serotonin release in the striatum and the motor activities increased not during but after immobilization stress.

Animals↗
PubMed1998

Changes in H3 influenza A virus receptor specificity during replication in humans.

Influenza A viruses of the H3 subtype caused the 1968 Hong Kong pandemic, the hemagglutinin (HA) gene being introduced into humans following a reassortment event with an avian virus. Receptor specificity and serum inhibitor sensitivity of the HA of influenza A viruses are linked to the host species. Human H3 viruses preferentially recognize N-acetyl sialic acid linked to galactose by alpha2,6 linkages (Neu5Acalpha2,6Gal) and are sensitive to serum inhibitors, whereas avian and equine viruses preferentially recognize Neu5Acalpha2,3Gal linkages and are resistant to serum inhibitors. We have examined the receptor specificity and serum inhibitor sensitivity of H3 human influenza A viruses from the time they were introduced into the human population to gain insight into the mechanism of viral molecular evolution and host tropism. All of the viruses were sensitive to neutralization and hemagglutination inhibition by horse serum. Early H3 viruses were resistant to pig and rabbit serum inhibitors. Viruses isolated after 1977 were uniformly sensitive to inhibition by pig and rabbit sera. The recognition of Neu5Acalpha2,3Gal or Neu5Acalpha2,6Gal linkages was not correlated with the serum sensitivity. These data showed that the receptor specificity of HA, measured as inhibitor sensitivity, has changed during replication in humans since its introduction from an avian virus.

Amino Acid Sequence↗
PubMed1998

Severe heat stroke associated with high plasma levels of plasminogen activator inhibitor 1.

In a 38-year-old man, severe heat stroke caused disseminated intravascular coagulation (DIC) associated with significantly elevated plasma plasminogen activator inhibitor 1 levels. Investigation of the effects of hyperthermia on coagulation and fibrinolysis showed, in apparent conflict with previous reports, a time lag between the initial hypercoagulable and hyperfibrinolytic response (within 24 hr) and hypofibrinolysis shown by a disproportionate increase of PAI-1 (after 24 h), which possibly occurs in correspondence with the recovery of vascular endothelial integrity. The patient was discharged without sequelae although computed tomography (CT) scans indicated the likelihood of venous infarction or posterior inferior cerebellar artery area infarction secondary to DIC.

Adult↗
PubMed1998

Effects of nicotine and footshock stress on dopamine release in the striatum and nucleus accumbens.

We have used a microdialysis technique to analyze the effects of nicotine administration on the release of dopamine in the striatum and the nucleus accumbens (NAC) in rats under footshock stress. In the striatum, neither chronic systemic nicotine administration alone nor stress alone changed the extent of dopamine release. During stress application, however, chronic nicotine administration significantly increased dopamine release. In the NAC, stress did not induce increase in dopamine release in rats given nicotine chronically. However, in rats subjected to stress alone, dopamine release in the NAC was significantly increased after stress. In the striatum, the local infusion of 1.0 mM nicotine increased dopamine release. Furthermore, stress significantly increased nicotine-induced dopamine release. The local infusion of 1.0 mM nicotine into the NAC significantly increased dopamine release, but the levels returned to the baseline 30 min later. On the other hand, stress alone induced the release of dopamine 30 min later and the combination of stress and nicotine induced the release of dopamine during the stress and the effects lasted for 30 min. These results suggest that the responses of nicotine-induced dopamine release were different in the striatum and in the NAC under the stress. Stress and nicotine (systematically or locally administered) induced an immediate effect on dopamine release in the striatum, but in the nucleus accumbens stress alone and the combination of stress and nicotine induced a lasting release of dopamine (DA).

Animals↗