Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 199 records · Page 11Linked to original sources

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↗

PubMed1998

Novel point mutations in the alphaIIb subunit (Phe289-->Ser, Glu324-->Lys and Gln747-->Pro) causing thrombasthenic phenotypes in four Japanese patients.

We analysed the molecular basis of Glanzmann thrombasthenia (GT) in four Japanese patients with type I or type II disease. Polymerase chain reaction (PCR) and subsequent direct sequencing of platelet RNA and genomic DNA revealed three single nucleotide substitutions of the alphaIIb gene, which were confirmed by allele-specific PCR or restriction analysis. One patient with type I GT had a T to C base substitution in exon 11 resulting in a Phe (TTT)-289 to Ser (TCT) mutation (F289S) of the subunit. Another type I patient had a G to A base substitution in exon 12 resulting in a Glu (GAA)-324 to Lys (AAA) mutation (E324K). Interestingly, two unrelated patients with type II GT shared an A to C base substitution in exon 2 3, a region previously not associated with GT, resulting in a Gln (CAA)-747 to Pro (CCA) mutation (Q747P). To analyse the effects of these mutations on alphaII(b)beta3 surface expression, the wild-type alphaIIb cDNA or mutant alphaIIb cDNAs were transfected into Chinese hamster ovary (CHO) cells together with a wild-type beta3 cDNA. Flow cytometric analysis using an anti-alphaII(b)beta3 complex antibody revealed that 50.6% of CHO cells with wild-type alphaII(b)beta3 expressed complexes, whereas only 1 6%, 7.7% and 31.3% of cells, with IIb(F289S)beta3, alphaIIb(E324K)beta3 and alphaIIb(Q747P)beta3 expressed complexes, respectively. Our data indicate that these three novel point mutations in the alphaIIb subunit may hamper surface expression of the alphaII(b)beta3 complex, thus resulting in the quantitative GT phenotypes of platelets from these patients.

Adult↗

PubMed1998

Distribution of nerve growth factor in cat brains following topical application of solution or Minipellet.

The distribution of nerve growth factor (NGF) was studied after topical application of NGF solution or NGF Minipellet into the caudate nucleus of cat brains. Each aliquot of NGF solution or a piece of NGF Minipellet contains 200 micrograms of mouse 2.5S beta-NGF. The concentrations of NGF in various areas of the brain were determined by enzyme-linked immunosolvent assay (ELISA). The tissue concentrations of NGF were very high at 6 h after injection of NGF solution (124.0 +/- 2.46 to 2144.0 +/- 16.03 ng g-1), but quickly decreased on day 1. The tissue concentrations of NGF were low at 6 h after implantation of NGF Minipellet, but were considerably increased on day 1 (11.22 +/- 3.36 to 72.04 +/- 20.45 ng g-1), and slowly decreased during the following 6 to 14 days. The present study demonstrates the temporal and spatial profiles of NGF distribution in the brain of middle-sized animals after topical application. Injection of NGF solution resulted in abrupt, but very transient, elevation of tissue NGF. Implantation of NGF Minipellet maintained the tissue NGF at biologically effective levels for 6 to 14 days.

Administration, Topical↗

PubMed1998

A bioassay for serum interferon based on induction of 2'5'-oligoadenylate synthetase activity.

We have developed a bioassay for interferons (IFN) based on measuring the amounts of 2',5' oligoadenylate synthetase (2-5AS) induced in cells of the THP-1 monocyte line in response to IFN. The assay can be completed in 20 h, gives reproducible results, and is at least 50 times more sensitive to IFN-alpha than conventional cytopathic effect inhibition antiviral assays. It is, respectively, less and much less sensitive to IFN-beta and IFN-gamma. The presence of preexisting 2-5AS activity in a sample does not influence the results. We have used this assay to measure very low levels (0.1-0.5 IU/ml) of endogenously formed IFN-alpha in serum samples from patients with various diseases and also to measure the residual small amounts of IFN-alpha still present in the serum as late as 48 h after an i.m. injection of 3 million IU, which is appreciably later than in previous methods. Thus, our highly sensitive assay offers considerable advantages, not least in relation to the clinical use of IFN.

2',5'-Oligoadenylate Synthetase↗

PubMed1998

Comparative evaluation of sialylated carbohydrate antigens, KL-6, CA19-9 and SLX as serum markers for interstitial pneumonia.

We compared diagnostic values of three serum carbohydrate antigens, KL-6, CA19-9 and SLX to discriminate interstitial pneumonia (IP) from alveolar pneumonia and healthy volunteers. Subjects consisted of 13 patients with idiopathic pulmonary fibrosis and 10 associated with collagen vascular diseases, 12 patients with sarcoidosis and 70 controls (52 healthy volunteers and 18 patients with alveolar pneumonia). Cut-off values were determined at the level at which the diagnostic accuracy became the highest for each marker, 449 U/mL for KL-6, 26 U/mL for CA19-9 and 41 U/mL for SLX. The sensitivity, the specificity and the diagnostic accuracy were 74.3% (26/35), 98.6% (69/70) and 90.5% (95/105) in KL-6, 42.9% (15/35), 94.3% (66/70) and 77.1% (81/105) in CA19-9, and 20.0% (7/35) and 95.7% (67/70) and 70.5% (74/105) in SLX, respectively. Receiver operating characteristic curves revealed that KL-6 was far superior to both CA19-9 and SLX. These results suggest that KL-6 is the best marker for interstitial pneumonia among these carbohydrate antigens.

Adult↗

PubMed1998

Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group.

PURPOSE: Irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC) as monotherapy. Cisplatin is also a key drug against SCLC. We conducted a phase II study of CPT-11 combined with cisplatin to evaluate the efficacy and toxicity of this regimen in patients with previously untreated SCLC. PATIENTS AND METHODS: Seventy-five patients with previously untreated SCLC were enrolled onto the study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1 every 28 days. Four courses of chemotherapy followed by thoracic irradiation were given to patients with limited disease (LD) and six courses to patients with extensive disease (ED). RESULTS: The overall response rate was 84%, with a complete response (CR) rate of 29%. Forty patients with LD achieved an overall response rate of 83% and a CR rate of 30% and 35 patients with ED achieved an overall response rate of 86% and a CR rate of 29%. The median response duration was 8.0 months for LD patients and 6.6 months for ED patients. The median survival was 14.3 months for LD patients and 13.0 months for ED patients. The major grade 3 or 4 toxicities were neutropenia (77%), leukopenia (45%), diarrhea (19%), and anemia (39%). Two patients died with concomitant neutropenia and diarrhea. CONCLUSION: This is a new active regimen for SCLC, especially ED-SCLC, with acceptable toxicity. A phase III study that compares CPT-11/cisplatin with etoposide/cisplatin for ED-SCLC is now being conducted.

Adult↗

PubMed1998

The 'ligand-induced conformational change' of alpha 5 beta 1 integrin. Relocation of alpha 5 subunit to uncover the beta 1 stalk region.

Integrin heterodimers undergo a conformational change upon the binding of ligand to their extracellular domains. An anti-beta1 integrin monoclonal antibody AG89 can detect such a conformational change since it recognizes a ligand-inducible epitope in the stalk-like region of beta1 subunits. The binding of a 125I-labeled AG89 Fab fragment to alpha5 beta1 integrins on K562 cells was assessed and analyzed by the Scatchard method. High affinity binding sites for AG89 are present on cells treated with ligand peptide. In addition, results revealed that cells treated with EDTA also express AG89 binding sites with the same affinity although the number of binding sites is 4-fold lower. AG89 immunoprecipitated alpha5 beta1 complexes from surface-labeled K562 cells treated with ligand peptide. By contrast, it immunoprecipitated only beta1 chains when the ligand peptide was absent, suggesting that high affinity binding sites on EDTA-treated cells are associated with non-functional beta1 monomer. Additional studies show that the epitope for AG89 is constitutively exposed on mutant beta1 that cannot complex with alpha5. These data suggest that the AG89 epitope is masked by the alpha5 subunit. Ligand binding and integrin activation may uncover the beta1 stalk region by triggering a conformational shift of alpha5 relative to beta1.

Animals↗

PubMed1998

Chinese hamster ovary cells expressing alpha4beta1 integrin stimulate osteoclast formation in vitro.

It is reported that Chinese hamster ovary cells transfected with human alpha4 cDNA (alpha4CHOs) and expressing functional alpha4beta1 integrin developed bone metasasis in nude mice. To clarify the role of alpha4beta1 integrin in bone metastasis, in terms of tumor-mediated bone destruction, we examined whether alpha4CHOs stimulate osteoclast formation in cocultures with mouse bone marrow cells. The number of osteoclast-like cells identified as tartrate-resistant acid phosphatase positive multinucleated cells (TRAP(+) MNCs) formed from bone marrow cells increased with the increasing number of alpha4CHOs cocultured. The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and prostaglandin E2 (PGE2) on TRAP(+) MNC formation were enhanced in cocultures with alpha4CHOs. TRAP(+) MNCs induced by alpha4CHOs possessed calcitonin receptors and resorbed calcified tissues. In cocultures, alpha4CHOs and bone marrow stromal cells were in contact with each other and bone marrow stromal cells expressed vascular cell adhesion molecule-1 (VCAM-1), which is one of the ligands for alpha4beta1 integrin. TRAP(+) MNC formation was not stimulated in cocultures where direct contact between alpha4CHOs and bone marrow cells was inhibited by membrane filters. Alpha4CHOs do not support TRAP(+) MNC formation in cocultures with spleen cells but do support TRAP(+) mononuclear cell and MNC formation from spleen cells in the presence of osteoblastic cells. Cultured media from alpha4CHOs, bone marrow cells, and cocultures of alpha4CHOs and bone marrow cells did not stimulate TRAP(+) MNC formation or enhance the effects of 1,25(OH)2D3 and PGE2 in bone marrow cultures. The concentrations of PGE2 and interleukin-6 (IL-6) in cultured media were not different between the cultures of bone marrow cells and the cocultures of bone marrow cells and alpha4CHOs. Anti-human alpha4 and anti-mouse VCAM-1 antibodies inhibited TRAP(+) MNC formation induced by alpha4CHOs. These results indicate that alpha4CHOs stimulated TRAP(+) MNC formation through direct cell-to-cell interaction between alpha4beta1 and VCAM-1. It is suggested that in addition to various soluble factors regulating osteoclast formation, cell-to-cell interaction between tumor cells and bone marrow cells is important for inducing osteoclasts at the site of bone metastasis and leading to bone destruction.

Acid Phosphatase↗

PubMed1998

Plasma levels of 5-HT and 5-HIAA increased after intestinal ischemia/reperfusion in rats.

Intestinal ischemia/reperfusion (I/R) causes serious systemic injury, mainly from a variety of bioactive substances released from the injured intestine. To assess the possible roles of serotonin (5-hydroxytryptamine, 5-HT), a bioactive amine mainly stored in the intestine, in I/R injury, we assayed the levels of tryptophan, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) in the blood and intestine in a rat I/R model. Plasma 5-HT increased significantly over time after reperfusion; the plateau level was obtained 4 h after reperfusion and was associated with an increase in 5-HIAA. Plasma tryptophan levels declined gradually after reperfusion. The ratio of 5-HIAA/5-HT was significantly higher in I/R rats than in control rats, suggesting that elevated 5-HT was quickly metabolized in the systemic circulation. In the intestine, 5-HT decreased dramatically, whereas tryptophan increased. This phenomenon was prominent in the severely damaged intestine. These findings suggest that the injured intestine released large amounts of 5-HT, whereas its synthesis in the injured intestine was suppressed. An increase in 5-HT in the circulation may be related to various circulatory disturbances observed in humans after intestinal ischemia.

5-Methoxytryptamine↗

PubMed1998

[Facilitation of tibialis anterior H reflex and depression of reciprocal Ia inhibition on soleus motoneurons during teeth-clenching in man].

Modulation of the tibialis anterior (T.A.) H reflex and the reciprocal Ia inhibition from the ankle flexor to the extensor were studied during voluntary teeth-clenching in 7 healthy adult volunteers to investigate the correlation between the oral motor activity and the somatic motor function. The T.A. H reflex was significantly facilitated during voluntary teeth-clenching, and the amount of this facilitation increased with the level of masseter EMG activity. Furthermore, the reciprocal Ia inhibition of the soleus H reflex, induced by stimulation of the common peroneal nerve at a subthreshold intensity for evoking the T.A. M wave, was significantly depressed during voluntary teeth-clenching. It was concluded that 1) the T.A. H reflex is facilitated during voluntary teeth-clenching, 2) there is a positive correlation between the amount of facilitation of the T.A. H reflex and the level of teeth-clenching force, and 3) the reciprocal Ia inhibition of the crural muscle is reduced during voluntary teeth-clenching. It was suggested that teeth-clenching contributes to stability of body stance by increasing the stiffness of the ankle joint.

Adult↗

PubMed1998

Treatment of intracranial abscess in the era of neuroimaging: an analysis of 13 consecutive cases.

We report a series of 13 consecutive patients with intracranial abscess treated at our institution since examination by computed tomography (CT) became available. After various treatments, all abscesses healed. CT has broadened the range of treatment options. Manual puncture was performed in most patients. Stereotactic aspiration through a burr hole, medical therapy alone, or complete excision, including the capsule, via craniotomy may be chosen in cases selected by CT analysis. Individualization of treatment in this disease has become increasingly valuable in effecting a cure.

Adolescent↗

PubMed1998

Pancreatic diseases: evaluation with MR cholangiopancreatography.

Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive diagnostic modality capable of producing high-quality images of the biliary tree and pancreatic duct. We evaluated the MRCP capability of depicting the normal pancreatic duct and, based on data achieved, studied the usefulness in the pathologic pancreatic duct. MRCP was performed in 42 patients without any pancreatic lesion and in 162 patients with pancreatic diseases, including congenital anomalies of biliary tree and pancreatic duct. Results were compared with endoscopic retrograde cholangiopancreatography (ERCP) in 93 patients. The visualization of the pancreatic duct and its branches and the presence or absence of dilatation, stenosis, and filling defects were recorded. All images were interpreted retrospectively and blindly by three radiologists. Among control patients, the main pancreatic duct (MPD) was depicted in the head, body, and tail of the pancreas in 41 (98%), 39 (93%), and 31 (74%), and accessory pancreatic duct and secondary branches in the head, body, and tail of the pancreas were depicted in 11 (26%), eight (19%), four (10%), and two (5%) of these patients. Compared with ERCP, MRCP overestimated the stenosis of MPD and underestimated the dilatation of the branches and filling defects in the pancreatic duct in pancreatic diseases, especially pancreatitis. However, MRCP was distinctly advantageous over ERCP in diagnosing mucin-producing tumor of the pancreas, cystic lesions, and depicting the whole, including the part distal to the obstructed site. Four of the eight cases of pancreas divisum, and 10 of the 12 cases of anomalous pancreaticobiliary duct union also were demonstrated. MRCP can accurately demonstrate the normal pancreatic duct as well as various pancreatic duct abnormalities, including congenital anomalies of the biliary tree and pancreatic duct.

Adolescent↗

PubMed1998

Prolonged hepatic warm ischemia in non-heart-beating donors: protective effects of FK506 and a platelet activating factor antagonist in porcine liver transplantation.

BACKGROUND: Prolonged warm ischemic injury in non-heart-beating donors (NHBDs) significantly affects hepatic allograft function after liver transplantation (LTx). METHODS: The effects of FK506 and the platelet activating factor antagonist E5880 on postoperative function of hepatic allografts procured from NHBDs were evaluated in porcine orthotopic LTx. In donors, livers were subjected to 90 minutes of warm ischemia and a subsequent 4-hour cold preservation. Group 1 (n = 6) was the untreated control group. In group 2 (n = 4), donors were pretreated with FK506 (0.3 mg/kg). In group 3 (n = 4), donors and recipients were treated with E5880 (0.3 mg/kg). In group 4 (n = 6), pigs were treated with both FK506 and E5880. RESULTS: All of the recipients in group 1 died within 12 hours. In groups 2 and 3, half of the recipients survived more than 12 hours. In group 4, all of the recipients survived more than 2 days (p < 0.01 compared with group 1). The improved survival seen in group 4 was associated with a reduction in the serum concentrations of glutamic oxaloacetic transaminase and lactate, and a restoration of hepatic energy charge. CONCLUSIONS: The present study suggests that FK506 and E5880 can improve the function of hepatic allografts subjected to prolonged warm ischemia in NHBDs, and that the protective effects of the two drugs seem to be synergistic.

Adenosine Triphosphate↗

PubMed1998

[Endoscopic findings of esophagitis in concurrent chemo-radiotherapy for lung cancer].

We performed esophageal endoscopy with concurrent chemo-radiotherapy for lung cancer in 19 patients. Endoscopical examination proved that seven patients (36.8%) had esophageal erosion or coating (grade 2), four patients (21.1%) had ulcer or bleeding (grade 3) confined to the radiation field, and only one patient (5.3%) had severe symptoms (WHO grade 3). There was a discrepancy between patients' symptoms and endoscopical findings. Endoscopically proven esophagitis, that is, erosion or coating (grade 2), and ulcer or bleeding (grade 3), was more frequent in the daily low-dose chemotherapy group (5/5) than in the full dose chemotherapy group (5/14) (p < 0.05). One patient with grade 3 endoscopial damage showed less recovery in spite of three months medication. In concurrent radiochemotherapy in which the radiation field includes the esophagus, careful attention should be given to radiation esophagitis, which may be underestimated when assessed on the basis of subjective symptoms alone. Therefore, endoscopy is recommended even if patients have few complaints, and once the esophageal ulcer is proven (grade 3), it should be closely followed up using endoscopy.

Adult↗

PubMed1998

Human thrombin and calcium bound factor Xa significantly shorten tPA-induced fibrin clot lysis time via neutralization of plasminogen activator inhibitor type 1 activity.

Employing a fibrin clot lysis assay, we reassessed the significance of the neutralization of plasminogen activator inhibitor type 1 (PAI-1) activity by thrombin and factor-Xa in fibrinolysis. When PAI-1 enriched fibrin clots were formed using increasing concentrations of thrombin (0.1, 0.5, 1.0 IU/ml), their lysis times became shorter (43.8 +/- 4.9, 25.7 +/- 3.7, 13.9 +/- 0.8 h respectively). Times were shortened further by either heparin (43.9 +/- 11.0, 12.1 +/- 2.6, 3.6 +/- 0.2 h respectively) or vitronectin (17.0 +/- 1.6, 1.9 +/- 0.7, 0.9 +/- 0.0 h respectively). Factor-Xa together with Ca++ shortened the clot lysis time further. Fibrin autography revealed that both enzymes dose dependently interfered with complex formation between tPA and PAI-1, making large amounts of tPA remaining to be free form. The mechanism seems to play a role in the coagulation associated enhancement of fibrinolysis.

Anticoagulants↗

PubMed1998

[Demonstration of normal bile duct and pancreatic duct with MR cholangiopancreatography].

Demonstration of normal bile duct and pancreatic duct with MR cholangiopancreatography was assessed in 78 patients including 19 cases of not impacted gallstone. Breath hold 2D-MRCP and intermittent breath hold 3D-MRCP was performed with half-Fourier fast spin echo technique using 1.5 T imager and surface coil. Diagnostic depiction rates of main pancreatic duct were 99% in the head, 97% in the body, and 91% in the tail, and of extrahepatic bile duct was 100%. Visualization of accessory pancreatic duct was 42%, but of side branch of pancreatic duct in the body to tail was poor. Anatomic variants of the biliary tree were seen in 15 cases. The reason of poor demonstration was the poor breath hold. In the majority of patients, MRCP can provide the accurate information of pancreaticobiliary tract without dilatation.

Adolescent↗

PubMed1997

Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress.

A cDNA library of human umbilical vein endothelial cells exposed to fluid shear stress was constructed to search for functional endothelial genes expressed under flow conditions, and cDNAs encoding members of the G protein-coupled receptor (GPCR) family were cloned by a polymerase chain reaction (PCR) method using degenerate oligonucleotide primers. One of the two GPCR clones obtained was edg-1, and the other clone is a novel gene named FEG-1 that encodes a 375-amino acid protein similar to the receptors for both angiotensin II and chemokines. Reverse transcriptase-PCR showed that the FEG-1 and edg-1 mRNA levels in endothelial cells increased markedly in response to fluid flow. This suggests that FEG-1 and edg-1 may be receptor genes that play important roles in the regulation of endothelial function under physiological blood flow conditions.

Amino Acid Sequence↗

PubMed1997

Echovirus 1 interaction with the human very late antigen-2 (integrin alpha2beta1) I domain. Identification of two independent virus contact sites distinct from the metal ion-dependent adhesion site.

The human integrin very late antigen (VLA)-2 (CD49b/CD29) mediates interactions with collagen and is the receptor for echovirus 1. Binding sites for both collagen and echovirus 1 have been mapped to the I domain within the alpha2 subunit of the VLA-2 alpha2beta1 heterodimer. Although murine VLA-2 interacts with collagen, it does not bind virus. We have used isolated human-murine chimeric I domains expressed as glutathione S-transferase fusion proteins in Escherichia coli to identify two groups of amino acids, 199-201 and 212-216, independently involved in virus attachment. These residues are distinct from the metal ion-dependent adhesion site previously demonstrated to be essential for VLA-2 interactions with collagen. Mutations in three metal ion-dependent adhesion site residues that abolish adhesion to collagen had no effect on virus binding. These results confirm that different sites within the I domain are responsible for VLA-2 interaction with extracellular matrix proteins and with viral ligands.

Amino Acid Sequence↗