Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 55 records · Page 3Linked to original sources

PubMed2000

Nicotine attenuates stress-induced changes in plasma amino acid concentrations and locomotor activity in rats.

It is known that stressor stimuli (both systemic and processive) and nicotine activate central nervous system. Surprisingly, numerous studies have demonstrated an increase in nicotine self-administration among smokers when exposed to stress in order to reduce the stress-related tension. Therefore, in the present study, we decided to investigate the influence of nicotine on both behavioral (i.e., on locomotor activity) and metabolic (i.e., on the level of amino acids in the plasma) changes following water immersion restraint stress in rats. As expected, the stress produced evident decline in locomotor activity of the rats (p < 0.001) and in the levels of all plasma amino acids studied (p < 0.05). Nicotine alone also significantly reduced locomotor activity (p < 0.05) and the levels of some plasma amino acids. However, when administered to rats subjected to water immersion and restraint, nicotine attenuated both stress-induced decrease in locomotor activity (p < 0.05) and in some plasma amino acids. Thus, this study demonstrated that the mode of action of nicotine is strongly dependent on the level of initial brain activity, which provide new evidence for arousal-modulation model of nicotine action.

Amino Acids↗

PubMed2000

A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter.

Dominantly inherited, late-onset pure cerebellar ataxia is a group of genetically heterogeneous neurodegenerative disorders. Approximately half of these disorders in the Japanese population are caused by moderate expansion of a CAG repeat in the coding region of the CACNA1A gene on chromosome 19p13 (SCA6). However, neither the loci nor the specific mutations for the remaining disorders have been determined. We performed systematic linkage analysis in a three-generation Japanese family with a locus or mutation that differed from those of known spinocerebellar ataxias. The family members with a late onset (> or =39 years old) exhibited pure cerebellar ataxia, whereas those with an early onset (< or =27 years old) first showed intermittent axial myoclonus followed by ataxia. Other neurological signs were sparse, and neuroimaging studies revealed that atrophy was confined to the cerebellum. Multipoint analysis and haplotype reconstruction ultimately traced this novel spinocerebellar ataxia locus (SCA14) to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter (Zmax = 4.08, corrected for age-dependent penetrance).

Adolescent↗

PubMed2000

Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese patients.

Twenty-four Japanese hypertensive patients of both sexes, grouped as having 'medium' and 'high' baseline total lipid values, had their serum lipids, lipoproteins and plasma fibrinolytic parameters, renin and noradrenaline levels determined after 3 months of amlodipine treatment. For the patients with 'medium baseline values', total plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex levels decreased, while the changes in lipids and lipoproteins were not significant after amlodipine treatment. For the patients with 'high baseline values', the mean triglyceride and very low density lipoprotein cholesterol (VLDLC) levels were reduced while the reductions in total and free PAI-1 and the increase in tissue plasminogen (t-PA) levels were not significant after amlodipine treatment. Negative correlations were observed between t-PA and high density lipoprotein cholesterol (HDLC) and HDLC/total cholesterol (TC) ratio in the patients with 'medium baseline values' while t-PA positively correlated with HDLC/TC ratio in patients with 'high baseline values'. The mean levels of renin and noradrenaline remained unchanged before and after amlodipine treatment in the two baseline groups. These findings show that baseline lipid levels of the hypertensive patients could influence lipids and fibrinolytic parameters differently during amlodipine treatment. The baseline lipid levels also influenced the metabolic association between lipids and fibrinolytic function in hypertensive patients during amlodipine treatment. The baseline total lipid values could therefore provide explanations for the complex metabolic interaction between lipids and fibrinolytic function as well as for the antiatherogenic actions of amlodipine treatment in hypertensive patients.

Aged↗

PubMed2000

Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during treatment of hypertension with cilnidipine.

Sixteen adult hypertensive patients of both sexes, classified as having 'medium' (total lipid profile 240-300 mg dl(-1)), and 'high' (total lipid profile >300 mg dl(-1)) baseline values, underwent serum lipids, lipoproteins and plasma fibrinolytic parameters evaluations after 3 months of cilnidipine treatment. Patients with 'medium baseline values' did not have any change in lipids, lipoproteins and fibrinolytic parameters while patients with 'high baseline values' had beneficial lipid and lipoprotein changes [decreases in total cholesterol (TC), triglycerides (TG), very low density lipoprotein-cholesterol (VLDLC) and increases in high density lipoprotein-cholesterol (HDLC), and HDLC/TC ratio] after cilnidipine treatment. Changes in lipids were negatively associated with fibrinolysis for the patients with 'medium baseline values' and positively associated in patients with 'high baseline values' after cilnidipine treatment. Reduction in blood pressure was related to fibrinolysis and reduced risk of coronary heart disease in the patients with 'high baseline values' after cilnidipine therapy. These results show that during cilnidipine treatment, the baseline lipid profile levels of the patients may influence the lipid altering actions as well as the interaction between lipids and fibrinolysis.

Aged↗

PubMed2000

Spontaneous and ethyl-nitrosourea-induced medullomyoblastomas in cerebellar vermis defect (CVD) mutant rats.

A 26-week-old female cerebellar vermis defect (CVD) rat, a mutant with cerebellar vermis defect and cerebellar dysplasia, developed a brain tumor about 10 mm in diameter. Histopathologically, the tumor consisted of diffuse proliferation of small round to ovoid cells with hyperchromatic nuclei, occasionally containing round to strap-shaped myoblastic cells. Immunohistochemically, the small round cells expressed neuron-specific enolase and synaptophysin, indicating neuronal differentiation; myoblastic components reacted to desmin, myoglobin, and vimentin. Based on these findings, the case was diagnosed as a medullomyoblastoma (MMB). Furthermore, two cerebella tumors in CVD rats, which were induced by transplacental application of ethyl-nitrosourea, showed histopathology similar to the aforementioned case. MMB is a very rare tumor in humans and animals; thus, it is noteworthy that MMBs developed in CVD rats, involving the dysplastic cerebellum with abnormal migration of external granule cells.

Animals↗

PubMed2000

Avian influenza virus intranasally inoculated infects the central nervous system of mice through the general visceral afferent nerve.

To define the route of influenza virus invasion into the central nervous system (CNS), an avian influenza A (H5N3) virus was inoculated into mice intranasally or intravenously. Only the intranasal infection group mice showed depression and retention of gas in the digestive system. Pathological findings in the animals were bronchointerstitial pneumonia and non-suppurative encephalitis restricted to the brain stem. The nerve nucleus primarily affected was the nucleus of solitary tract. Prior to the development of the CNS lesions, viral antigen was detected in vagal and trigeminal ganglia. These results suggest that the primarily replicated virus in the respiratory mucosa ascended to the CNS via sensory nerve routes, inducing lesions in the brain stem, and then spread trans-synaptically in the CNS.

Animals↗

PubMed2000

Precursor genes of future pandemic influenza viruses are perpetuated in ducks nesting in Siberia.

Influenza A viruses of different subtypes were isolated from fecal samples of ducks in their nesting areas in Siberia in summer from 1996 to 1998. Phylogenetic analysis of the NP genes of the isolates in Siberia and those in Hokkaido, Japan on their flyway of migration from Siberia to the south in autumn revealed that they belong to the Eurasian lineage of avian influenza viruses. It is noted that the genes of the isolates in Siberia are closely related to those of H5N1 influenza virus strains isolated from chickens and humans in Hong Kong in 1997 as well as to those of isolates from domestic birds in southern China. The results indicate that influenza viruses perpetuated in ducks nesting in Siberia should have contributed genes in the emergence of the H5N1 virus in Hong Kong. Vaccine prepared from avirulent A/duck/Hokkaido/4/96 (H5N3) influenza virus was potent enough to protect mice from challenge with lethal dose of the pathogenic H5N1 virus [19]. Intensive surveillance study of aquatic birds especially in Siberia is, therefore, stressed to provide information on the future pandemic influenza virus strains and for vaccine preparation.

Animals↗

PubMed2000

Structure of the infected cell protein 0 gene of canine herpesvirus.

The canine herpesvirus infected cell protein 0 (CICP0) gene was sequenced. The CICP0 gene was transcribed as a 1.4 kb mRNA from the end of the unique long region nearby the internal repeat during early phase of productive infection of the virus. An open reading frame of the gene encodes a polypeptide of 333 amino acids. The RING finger domain and acidic transcriptional activation domain were found at the N-terminus and within the middle region in the deduced amino acid sequence, respectively, suggesting that the CICP0, like the ICP0 of herpes simplex virus 1, is a transactivating protein.

Amino Acid Sequence↗

PubMed2000

Serotonergic and kynurenic pathways in rats exposed to foot shock.

Electric foot shock was applied to rats and levels of tryptophan and its metabolites were measured in the plasma, central nervous system and peripheral tissues. Metabolites of tryptophan are the results of the enhancement of serotonergic and kynurenine pathways. Plasma levels of tryptophan increased significantly immediately after the foot shock and returned to normal values within 24 h. Tryptophan levels also increased in all the brain areas immediately after stress application and returned to normal values within 24 h. Foot shock elevated the levels of kynurenine in the plasma, liver, kidney and every parts of the brain. 3-Hydroxykynurenine and kynurenic acid levels were increased in the brain. The present observations suggest that stress activates not only serotonergic pathway but also kynurenine pathway in the central nervous system and periphery. Some metabolites of kynurenine pathway, such as 3-hydroxykynurenine, are neurotoxic while other metabolite, such as kynurenic acid, may be neuroprotective. Increase in serotonin level in the hypothalamus and midbrain stabilises emotion and prevents mood disorders. Therefore, some brain dysfunction resulting from stress may be prevented by the metabolites of tryptophan. The balance of these functions may be important in the maintenance of nerve integrity under stress conditions.

Animals↗

PubMed2000

Fatal cardiovascular injuries to the unbelted occupant associated with airbag deployment: two case-reports.

We present two forensic autopsy cases of unbelted occupants associated with the airbag deployment in motor vehicle collisions. Both victims suffered from cardiovascular injuries which were the cause of death. Case 1: A 50-year-old man sustained a contusion on the left anterior chest with rib fractures and laceration of the intrapericardial inferior vena cava, the right ventricle, and the right pleuropericardium. Case 2: A 40-year-old man sustained multiple rib fractures, sternal fracture, and the rupture of the right ventricle. Autopsies and vehicle examinations revealed that both victims' chest seemed to strike the steering wheel through the deployed airbag. Therefore, we determined that the source of blunt impact force is the steering wheel through the airbag rather than airbag deployment only. In light of these two cases, we learned that the steering wheel should be considered as the blunt impact force inducing cardiovascular injuries even in cases in which the airbag has been deployed.

Journal Article↗

PubMed2000

Brain net unidirectional uptake of alpha-[14c]methyl-L-tryptophan (alpha-MTrp) and its correlation with regional serotonin synthesis, tryptophan incorporation into proteins, and permeability surface area products of tryptophan and alpha-MTrp.

The uptake and trapping constants for labeled tryptophan (Trp) via the serotonin (5-hydroxytryptamine; 5-HT) metabolic pathway and for the incorporation of Trp into proteins, and alpha-[14C]methyl-L-tryptophan (alpha-MTrp) were measured. Measurements were done in rats treated with either saline or probenecid (200 mg/kg). In addition, the blood-brain barrier (BBB) permeability surface area products for Trp (PS(T)) and alpha-MTrp (PSalpha) were measured in normal rats. The results suggest that, in both groups of rats, there is a highly significant correlation (p < 0.05; Pearson Product Moment Correlation (PPMC) between the brain uptake and trapping constants for alpha-MTrp and those of Trp via the 5-HT metabolic pathway, but there is no significant correlation (p > 0.05; PPMC) between either of these constants and the PS products of either compound. There is also no significant correlation (p > 0.05; PPMC) between the constant for the Trp incorporation into proteins with any of the other parameters. For all parameters, except Trp incorporation into proteins (alpha-MTrp is not incorporated into proteins), there was a highly significant correlation (p < 0.001) between the quantities measured for Trp and alpha-MTrp. The data presented here strongly suggests that the brain uptake and trapping of alpha-MTrp relates to brain 5-HT synthesis, and does not relate to the BBB transport or protein incorporation of Trp. On the basis of these results, as well as those previously reported, we concluded that trapping (unidirectional uptake) of alpha-MTrp can be converted to the 5-HT synthesis rates in the brain. From this also follows that labeled alpha-MTrp is a good tracer for in vivo evaluation of the brain 5-HT synthesis.

Animals↗

PubMed2000

Coagulation-associated enhancement of fibrinolytic activity via a neutralization of PAI-1 activity.

Total fibrinolytic activity in the vasculature is finely tuned by the balance between tissue plasminogen activator and plasminogen activator inhibitor type 1 (PAI-1). Although PAI-1 targets plasminogen activators, it also reacts with other serine proteases such as thrombin and factor Xa. The latter was shown to interact with PAI-1 only when a physiological concentration of calcium ions (Ca++) is present. Through such interaction, thrombin and Ca++-bound factor Xa shortened fibrin clot lysis times in a purified system by neutralizing PAI-1 activity. Both unfractionated heparin and vitronectin were shown to enhance the clot lysis further. Together with the cleavage and inactivation of PAI-1 by human neutrophil elastase, which was reported previously from our laboratory, such neutralization of PAI-1 activity by these serine proteases was shown to be strongly involved in the coagulation-associated enhancement of fibrinolytic activity.

Anticoagulants↗

PubMed2000

Neutrophil elastase may play a key role in developing symptomatic disseminated intravascular coagulation and multiple organ failure in patients with head injury.

OBJECTIVE: To study the mechanism associated with the development of symptomatic disseminated intravascular coagulation (DIC) after head injury. METHODS: Plasma parameters were analyzed in patients with symptomatic (group A, n = 10) and asymptomatic DIC (group B, n = 15) induced by head injury, and in patients in whom DIC was caused by sepsis (group C, n = 10). RESULTS: Levels of fibrinogen, alpha2PI-plasmin complex and platelets in group A (58.1 mg/dL, 22.4 microg/mL, 16.0 x 10(4)/ mm3) and group B (98.3, 22.1, 16.6 x 10(4)) were comparable, but differed significantly from those in group C (297.4, 2.4, 6.3 x 10(4)). Significant differences were observed between groups A and B in both neutrophil-elastase (1,528 vs. 293 microg/ml) and D-dimer (42.1 vs. 17.6 microg/mL). CONCLUSION: Neutrophil elastase may be implicated in the development of symptomatic DIC after head injury, whose characteristics include "enhanced fibrinolysis with minimal platelet loss."

Adolescent↗

PubMed2000

Recognition of N-glycolylneuraminic acid linked to galactose by the alpha2,3 linkage is associated with intestinal replication of influenza A virus in ducks.

The hemagglutinin (HA) of H3 human influenza viruses does not support viral replication in duck intestine despite its avian origin. A Leu-to-Gln mutation at position 226 and a Ser-to-Gly mutation at position 228 in the HA of human A/Udorn/307/72 (H3N2) permit a reassortant virus [human Udorn HA, with all other genes from A/mallard/New York/6750/78 (H2N2)] to replicate in ducks. To understand the molecular basis of this change in host range restriction, we investigated the receptor specificity of duck influenza viruses as well as of human-duck virus reassortants. The results indicate that the recognition of a glycoconjugate moiety possessing N-glycolneuramic acid (NeuGc) linked to galactose by the alpha2,3 linkage (NeuGcalpha2,3Gal) is associated with viral replication in duck intestine. Immunofluorescence assays with NeuGcalpha2,3Gal-specific antiserum detected this moiety primarily on the crypt epithelial cells of duck colon. Such recognition, together with biochemical evidence of NeuGc in crypt cells, correlated exactly with the ability of the virus to replicate in duck colon. These results suggest that recognition of the NeuGcalpha2,3-Gal moiety plays an important role in the enterotropism of avian influenza viruses.

Animals↗

PubMed2000

Functional importance of the coiled-coil of the Ebola virus glycoprotein.

Ebola virus contains a single glycoprotein (GP) that is responsible for receptor binding and membrane fusion and is proteolytically cleaved into disulfide-linked GP1 and GP2 subunits. The GP2 subunit possesses a coiled-coil motif, which plays an important role in the oligomerization and fusion activity of other viral GPs. To determine the functional significance of the coiled-coil motif of GP2, we examined the effects of peptides corresponding to the coiled-coil motif of GP2 on the infectivity of a mutant vesicular stomatitis virus (lacking the receptor-binding/fusion protein) pseudotyped with the Ebola virus GP. A peptide corresponding to the C-terminal helix reduced the infectivity of the pseudotyped virus. We next introduced alanine substitutions into hydrophobic residues in the coiled-coil motif to identify residues important for GP function. None of the substitutions affected GP oligomerization, but some mutations, two in the N-terminal helix and all in the C-terminal helix, reduced the ability of GP to confer infectivity to the mutant vesicular stomatitis virus without affecting the transport of GP to the cell surface, its incorporation into virions, and the production of virus particles. These results indicate that the coiled-coil motif of GP2 plays an important role in facilitating the entry of Ebola virus into host cells and that peptides corresponding to this region could act as efficient antiviral agents.

Amino Acid Motifs↗

PubMed2000

The cleavage and inactivation of plasminogen activator inhibitor type 1 and alpha2-antiplasmin by reptilase, a thrombin-like venom enzyme.

Reptilase, defibrase and ancrod are thrombin-like venom enzymes that cleave fibrinogen to release fibrinopeptide-A and generate fibrin monomers. Although these enzymes decrease fibrinogen levels in vivo, presumably by enhancing fibrinolytic activity, the mechanism has not been identified. In the present study, we analyzed their effects on the inhibitors of fibrinolysis. Plasminogen activator inhibitor-1 (PAI-1) was cleaved at its C-terminus by reptilase and lost its specific activity. Alpha2-antiplasmin (alpha2-AP) was cleaved both at the Pro19-Leu20 peptide bond and at its C-terminus by reptilase, and also lost its specific activity. The apparent second-order rate constants (mol/l per min per Batroxobin unit) were 0.22 for the cleavage of PAI-1 (3.2 micromol/l) and 0.19 for that of alpha2AP (6.4 micromol/l), which were approximately 200-fold lower than that (47.0) for the cleavage of fibrinogen (1.1 micromol/l). Neither defibrase nor ancrod cleaved and inactivated these inhibitors. Only reptilase enhanced euglobulin clot lysis in vitro at high concentration, due probably to PAI-1 inactivation. Since all these three enzymes enhance fibrinolysis similarly during defibrination therapy, the neutralization or inactivation of the inhibitors of fibrinolysis appeared not to represent the main mechanism for the enhancement.

Ancrod↗

PubMed2000

Effects of cilnidipine on lipids, lipoproteins and fibrinolytic system in hypertensive patients.

Sixteen Japanese patients of both sexes aged 46-78 years with essential hypertension were studied at the cardiac clinic of the Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan. Serum lipids, lipoproteins, plasma fibrinolytic parameters, renin and noradrenaline were determined before and after 3 months of cilnidipine treatment. Systolic and diastolic blood pressures and heart rate were reduced while renin and noradrenaline levels remained unchanged after cilnidipine treatment. Total cholesterol and tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex were reduced. Changes in the other lipids, lipoproteins and fibrinolytic parameters were not significant after cilnidipine treatment. A negative correlation was found between low-density lipoprotein cholesterol and t-PA antigen levels after cilnidipine treatment. In conclusion, cilnidipine was effective for the treatment of hypertension and did not cause reflex tachycardia in Japanese patients. Cilnidipine treatment produced a beneficial lipid profile (decrease in total cholesterol), but did not show a consistent effect on fibrinolytic parameters in hypertensive patients. The metabolic interaction between beneficial lipid changes and fibrinolysis will be of value to better our understanding of the antiatherogenic effects of cilnidipine treatment in hypertensive patients.

Aged↗

PubMed1999

Negative regulatory role of the Escherichia coli hfq gene in cell division.

We found that the hfq::cat mutant strain produced minicells at high frequency. Minicell production by the mutant strain was more prominent in poor media and in the stationary phase than in rich media and in the exponentially growing phase. The amount of the cell division protein FtsZ increased up to two- to threefold of the wild-type cells in the hfq::cat mutant in the stationary phase, while such differences were not observed in the exponentially growing phase. Increased ftsZ mRNA levels were also observed in the hfq::cat mutant in the stationary phase. These results suggest a negative regulatory role of the DNA-, RNA-binding protein Hfq in cell division in the stationary phase.

Bacterial Proteins↗