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T Hiraki

Publications and source records attributed to T Hiraki.

At least 19 recordsLinked to original sources

c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK.

Using a yeast two-hybrid method, we searched for amyloid precursor protein (APP)-interacting molecules by screening mouse and human brain libraries. In addition to known interacting proteins containing a phosphotyrosine-interaction-domain (PID)-Fe65, Fe65L, Fe65L2, X11, and mDab1, we identified, as a novel APP-interacting molecule, a PID-containing isoform of mouse JNK-interacting protein-1 (JIP-1b) and its human homolog IB1, the established scaffold proteins for JNK. The APP amino acids Tyr(682), Asn(684), and Tyr(687) in the G(681)YENPTY(687) region were all essential for APP/JIP-1b interaction, but neither Tyr(653) nor Thr(668) was necessary. APP-interacting ability was specific for this additional isoform containing PID and was shared by both human and mouse homologs. JIP-1b expressed by mammalian cells was efficiently precipitated by the cytoplasmic domain of APP in the extreme Gly(681)-Asn(695) domain-dependent manner. Reciprocally, both full-length wild-type and familial Alzheimer's disease mutant APPs were precipitated by PID-containing JIP constructs. Antibodies raised against the N and C termini of JIP-1b coprecipitated JIP-1b and wild-type or mutant APP in non-neuronal and neuronal cells. Moreover, human JNK1beta1 formed a complex with APP in a JIP-1b-dependent manner. Confocal microscopic examination demonstrated that APP and JIP-1b share similar subcellular localization in transfected cells. These data indicate that JIP-1b/IB1 scaffolds APP with JNK, providing a novel insight into the role of the JNK scaffold protein as an interface of APP with intracellular functional molecules.

Adaptor Proteins, Signal Transducing↗

Secreted Abeta does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein.

Antibodies against APP, a precursor of Abeta deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Abeta mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Abeta40 and Abeta42 in the cultured media were undetectable by an assay capable of detecting 100 nM Abeta peptides. However, exogenously treated Abeta1-42 or Abeta1-43 required >3 microM to exert neurotoxicity, and 25 microM Abeta1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Abeta1-42, whereas serum attenuated toxicity by Abeta1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His(657)-Lys(676), but not the Abeta1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Abeta.

Alzheimer Disease↗

Insulin-like growth factor I (IGF-I) protects cells from apoptosis by Alzheimer's V642I mutant amyloid precursor protein through IGF-I receptor in an IGF-binding protein-sensitive manner.

It has been found that insulin-like growth factor I (IGF-I) exerts cytoprotection against Abeta amyloid-induced neuronal cell death. Deposits of Abeta amyloid are one of the pathological hallmarks of Alzheimer's disease (AD). Here, we examined whether IGF-I exerts protective activity against cell death induced by a familial AD (FAD)-linked mutant of amyloid precursor protein (APP), and we found that IGF-I protected cells from toxicity of FAD-associated V642I mutant of APP in multiple cell systems. IGFBP-3 blocked this action of IGF-I, but not of des(1-3)IGF-I, which was as active as IGF-I in the presence of IGFBP-3. The data also demonstrated that the IGF-I receptor (IGF-IR) mediates the protective activity of IGF-I. The antagonizing function of the IGF-I/IGF-IR system against V642I-APP, which is further antagonized by IGFBP-3, provides a molecular clue to the understanding of AD pathophysiology and to the establishment of potential therapy for AD.

Amino Acid Substitution↗

Altered hepatic hemodynamics caused by temporary occlusion of the right hepatic vein: evaluation with Doppler US in 14 patients.

PURPOSE: To evaluate with Doppler ultrasonography (US) the altered hepatic hemodynamics caused by temporary occlusion of the right hepatic vein. MATERIALS AND METHODS: The study group consisted of 14 patients being considered for hepatic arterial infusion or transarterial embolization. In all patients, maximum peak velocity of the blood flow in the right portal vein was measured with Doppler US before and during the occlusion of the right hepatic vein. In 13 patients, color Doppler US was performed to evaluate Doppler signal in the portal venous branch in the occluded area before and during occlusion. Average peak velocity in the right hepatic artery in eight patients was measured by using a transducer-tipped guide wire before and during occlusion. RESULTS: Maximum peak velocity of the right portal vein significantly decreased with occlusion (P <.01). Hepatic venous occlusion changed the Doppler signal in the portal venous branch in the occluded area from hepatopetal to no signal in 10 patients; to weakened hepatopetal in two; and to hepatofugal in one. Average peak velocity of the right hepatic artery showed a decrease or plateau for 15-30 seconds after the start of occlusion and then a rapid increase to reach a plateau at around 75-90 seconds, with 1.5-2 times as much velocity as that before occlusion. CONCLUSION: Increase in hepatic arterial velocity is accompanied by a decrease in the portal velocity with temporary occlusion of the right hepatic vein; the expected increased drainage through the portal vein was almost undetectable.

Aged↗

[Anesthetic management of a patient with a history of acute intermittent porphyria and an elevation of urinary porphobilinogen].

A 55 year-old female with a history of acute intermittent porphyria (AIP) in her twenties was scheduled for left total hip replacement. The clinical symptoms had been mild for the past 30 years, with occasional appearance of muscular weakness in the extremities. Porphyric symptoms were not apparent on the pre-operative round, but urinary porphobilinogen (PBG) was elevated on the pre-operative examination. Anesthesia was induced with propofol and the trachea was intubated by use of suxamethonium. Anesthesia was maintained with inhalation of 1.5-2.0% isoflurane and 50% N2O in O2. Twenty ml of 1% mepivacaine was injected around the wound at the completion of surgery. It was effective for postoperative pain control. We could successfully manage the patient during the intra- and post-operative periods without appearance of porphyric symptoms and increases of PBG and delta-aminolevulinic acid.

Anesthesia, General↗

Analysis of Galpha protein recognition profiles of angiotensin II receptors using chimeric Galpha proteins.

Receptors with a heptahelical structure initiate signal transduction by interacting with specific Galpha proteins. The aim of this study was to analyze the ability of type 1 (AT1) and type 2 (AT2) angiotensin receptors to recognize the receptor coupling regions of Galpha proteins using our previously described technique (Ikezu, T., Okamoto, T., Komatsuzaki, K., Matsui, T., Martyn, J.A.J., Nishimoto, I., 1996. Negative transactivation of cAMP response element by familial Alzheimer's mutants of APP. EMBO J. 15, 2468-2475; Komatsuzaki, K., Murayama, Y., Giambarella, U., Ogata, E., Seino, S., Nishimoto, I., 1996. A novel system that reports the G-proteins linked to a given receptor: a study of the type 3 somatostatin receptor. FEBS Lett. 406, 165-170). Chimeric Galphas protein constructs, whose receptor binding regions contained sequences from the four major families of Galpha proteins (Galphaq, Galphai, Galpha12, Galphas), were cotransfected with AT1 or AT2 receptors in COS cells, then stimulated with angiotensin II (Ang II). Changes in cellular cAMP were assayed on cell lysates by enzyme immunoassay. In the case of the Galphaq family, cotransfection of AT1 with Galpha11/Galphas, Galpha14/Galphas, Galpha16/Galphas, elicited significant increases in cAMP after agonist stimulation. Confirmatory results were found using an independent [35S]GTPgammaS binding assay. Further examination using chimeric G proteins for Galpha12 proteins and Galphai family proteins provided evidence that the AT1 receptor can recognize sequences from Galpha12, Galphai1/i2, Galphaz, Galphao, while both receptors interacted with Galphai3. These results provide a Galpha protein recognition database for both AT1 and AT2 receptors, which may be important for understanding the full spectrum of cellular responses mediated by the hormone Ang II.

3T3 Cells↗

Single oral administration of pilsicainide versus infusion of disopyramide for termination of paroxysmal atrial fibrillation: a multicenter trial.

A single oral dose of pilsicainide (PLS) is effective in terminating acute-onset atrial fibrillation (AF). However, the effectiveness of this single oral treatment has not been compared with the infusion of other antiarrhythmic drugs. The effects of a single oral dose of PLS on the termination of AF were compared with an infusion of disopyramide (DISO) in a multicenter trial. Seventy-two patients with electrocardiographically confirmed, symptomatic, paroxysmal AF (< 48-hour duration) were randomized to receive either a single 100- to 150-mg dose of PLS versus a 2 mg/kg (maximum dose = 100 mg) infusion of DISO. Successful defibrillation was defined as termination of AF within 2 hours of drug administration. Conversion of AF to sinus rhythm was achieved within 2 hours in 29 of 40 patients (73%) treated with PLS, and in 18 of 32 patients (56%) treated with DISO (NS). The mean time to return of sinus rhythm was 60 +/- 30 minutes in the PLS group versus 23 +/- 18 minutes in the DISO group (P < 0.001). DISO was particularly effective in terminating nocturnal AF, whereas PLS had a stable circadian effect. PLS was significantly more effective than DISO between 6 AM and 12 PM (64% vs 17%, P < 0.05). No adverse effect was observed in either group. In conclusion, a single oral dose of PLS was as effective as an infusion of DISO to restore sinus rhythm in patients with recent-onset AF. PLS consistently terminated AF regardless of its time of onset.

Administration, Oral↗

[Intraoperative hemodilutional autotransfusion using a closed circuit for patients of Jehovah's Witness].

We conducted hemodilutional autotransfusion using a closed circuit combined with a cell washing reinfusing system (Cell Saver) for two surgical patients of Jehovah's Witness. One was a 12 yr-old boy for extirpation of the teratoma in the anterior mediastinum and another was a 44 yr-old woman for left total hip replacement. The patients and their relatives had consented to the use of blood substitutes, hemodilutional autotransfusion using a closed circuit and Cell Saver. We devised a closed circuit system for hemodilutional autotransfusion combined with Cell Saver, in which two pumps for blood transfusion were used; one was for drawing blood from the femoral or the internal jugular vein and the other for returning blood to the peripheral vein. Blood volume in a bag interposed in the closed circuit was easily controlled by adjusting the speed of each pump. Blood collected from the surgical field by Cell Saver was also led to the bag. Acid citrate dextrose solution was infused into the closed circuit from the site close to the blood drawing. Both of our surgical patients were safely managed without homologus blood transfusion, although there remained some problems concerning the use of anticoagulants.

Adult↗

[Biopsy].

We reviewed the current devices, techniques, guiding images, indications and complications of needle biopsy with CT guidance. The development of new devices such as automated cutting needle has enabled radiologists to obtain tissue specimens of good quality at biopsy. Techniques such as the tandem or coaxial method ensure more a more accurate biopsy route. And helical CT and CT fluoroscopy have markedly shortened the time required for needle biopsy. However, we sometimes encounter minor complications, and rarely major ones, during and after needle biopsy. Some of these complications may be caused by malpractice. Therefore it is important always to pay attention to the possibility of complications of needle biopsy and to minimize radiation exposures from CT fluoroscopy.

Biopsy, Needle↗

Relationship between the biodistributions of radioactive metal nuclides in tumor tissue and the physicochemical properties of these metal ions.

This study was undertaken to elucidate the relationship between the biodistribution of radioactive metal nuclides in tumor tissue and its physicochemical properties. Potassium analogs (86Rb, 134Cs, 201Tl) were taken up into viable tumor tissue, although 22Na concentrated in necrotic tumor tissue. 67Ga and 111In were more predominant in inflammatory tissue than in the viable and necrotic tumor tissue. 169Yb and 167Tm accumulated in viable tumor tissue and tissue containing viable and necrotic tumor tissue. 67Ga, 111In, 169Yb and 167Tm were bound to the acid mucopolysaccharide with a mol. wt. of about 10,000 daltons in the tumor tissue. 46Sc, 51Cr, 95Zr, 181Hf, 95Nb, 182Ta, and 103Ru were highly concentrated in inflammatory tissue and were bound to the acid mucopolysaccharides with a mol. wt. exceeding 40,000 daltons. 65Zn and 103Pd concentrated in viable tumor tissue and were bound to the protein in the tissue. The results suggest that the difference in intra-tumor distribution of these elements is caused by a difference in the binding substances (or status) of these elements in the tissues, and the binding substance is determined by physicochemical properties of the elements. We therefore conclude that the biodistribution of radioactive metal ions in tumor tissue is determined by its own physicochemical properties.

Animals↗

Spatial differences of chemical features of atmospheric deposition between rainy season and winter in the areas facing to the Japan Sea, Japan

Atmospheric deposition was collected using filtrating bulk samplers at 32 sites in the areas facing to the Japan Sea (AFJS) from April 1991 to March 1994. The data were analyzed for winter (January and February) and the rainy season (June and July) when the climate is just the opposite. The AFJS was geographically divided into five areas, that is western Tohoku (WT), Hokuriku (HR), eastern San-in (ES), western San-in (WS) and northern Kyushu (NK). WT, HR and ES receive more precipitation than other regions in winter. H+ depositions increase in winter except NK. This is mainly due to high winter H+ concentrations. In spite of large amounts of precipitation in WT, HR and ES in winter, nss-SO4(2-) concentration was nearly equal to the average throughout Japan. Namely, nss-SO4(2-) depositions in these areas were nearly twice the national mean. In WT, HR and ES, nss-Ca2+ concentrations in winter are lower than the average of the whole country (less than the half). This may be the cause of the lower potentials of neutralization and the higher remaining acid concentrations in WT, HR and ES than NK and WS.

Journal Article↗

Detection of concealed left sided accessory atrioventricular pathway by P wave signal averaged electrocardiogram.

OBJECTIVES: The purpose of this study was to examine whether P wave signal-averaged electrocardiogram (P-SAECG), which detects subtle changes in P wave, detects the concealed accessory atrioventricular pathway (AP). BACKGROUND: It is difficult to differentiate atrioventricular reciprocating tachycardia (AVRT) due to the AP from atrioventricular nodal reentrant tachycardia (AVNRT) when the ventricular preexcitation is absent on 12-lead electrocardiograms. By electrophysiological studies, the anterograde conduction in the concealed AP is shown to be blocked near the AP-ventricular interface during sinus rhythm. METHODS: P-SAECG during sinus rhythm was performed in 20 normal volunteers (control), 21 patients with AVRT due to the concealed AP, 19 with AVNRT, 22 with paroxysmal atrial fibrillation (PAF), and 7 with automatic atrial tachycardia (AT). The filtered P wave duration (FPD) and AR20 (power spectrum area ratio of 0-20 to 20-100 Hz) were measured and repeated in AVRT, AVNRT and AT groups at one week after catheter ablation. RESULTS: The anterograde conduction in the concealed left-sided AP was confirmed in all cases by an electrophysiological study. The FPD in AVRT group was more prolonged than that in controls or AVNRT group. Although the FPD was similar between AVRT and PAF groups, AR20 differentiated between the two groups. Ablation of the concealed AP shortened FPD in AVRT group but that of the slow pathway or the atrial focus did not shorten in the AVNRT or AT groups, respectively. The changes in FPD after ablation were correlated with those in the duration of atrial activity by an electrophysiological study (r=0.67). CONCLUSIONS: Our findings suggest that P-SAECG detects the concealed left-sided AP, providing a clinical tool in noninvasively assessing atrial activation patterns.

Adolescent↗

Dispersion of filtered P wave duration by P wave signal-averaged ECG mapping system: its usefulness for determining efficacy of disopyramide on paroxysmal atrial fibrillation.

INTRODUCTION: Although it is desirable to know drug efficacy before initiating antiarrhythmic therapy, there have been no methods for this evaluation. P wave signal-averaged ECG (P-SAECG) is useful to detect subtle changes in disturbance of atrial conduction. The purpose of this present study was to test whether P-SAECG mapping system would give any information on the efficacy of disopyramide on the prevention of paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: P-SAECG was performed before disopyramide treatment, at 3 hours after a single dose of oral disopyramide (200 mg), and after 4 weeks of disopyramide treatment (300 mg/day). After measuring the filtered P wave duration by the vector magnitude and mapping methods, we calculated filtered P wave duration dispersion, difference between the maximal and minimal filtered P wave duration within 16 chest leads at these three time points. Filtered P wave duration and filtered P wave duration dispersion before treatment were longer in 32 patients with symptomatic PAF than in 31 healthy volunteers. Disopyramide was effective for suppression of PAF in 17 patients and ineffective in 15 patients after 4 weeks of treatment. Filtered P wave duration was similarly prolonged at 3 hours in the two groups, whereas filtered P wave duration dispersion at 3 hours after the disopyramide administration behaved differently; it decreased in all of the effective group and increased in all of the ineffective group. The effective patients were prospectively followed with the same treatment for 6 months. In 16 (94%) of these 17 effective patients, no PAF was documented and they remained to be asymptomatic. CONCLUSIONS: Thus, measuring filtered P wave duration dispersion with the P-SAECG mapping method after a single administration may predict the long-term efficacy of disopyramide in patients with PAF.

Administration, Oral↗

Frequency- and time-domain analysis of P wave in patients with paroxysmal atrial fibrillation.

We investigated the usefulness of the time- and frequency-domain analysis of the P wave triggered signal-averaged ECG (P-SAECG) for detecting patients with paroxysmal atrial fibrillation (Paf). In previous studies, the usefulness of the time domain of the P-SAECG to detect patients with Paf was described but that of the frequency domain is unknown. We analyzed the P-SAECG in the time and frequency domain in 23 patients with Paf and 19 controls. The 32-unipolar chest lead ECGs and the standard bipolar limb lead ECGs were obtained. The time-domain analysis showed that the filtered P duration (fPd) was significantly longer (P < 0.01) in patients with Paf than controls: the predictive accuracy of Paf with fPd > 120 ms was 69%. The frequency domain analysis showed that the area ratio of power spectrum area of 0-20 Hz to 20-100 Hz (AR20) was significantly higher (P < 0.01) and the magnitude ratio at 30 Hz (%Mag.30) calculated by dividing the magnitude at 30 Hz by the maximal magnitude was significantly (P < 0.01) lower in patients with Paf than controls in the left lateral chest leads. The predictive accuracy of Paf with AR20 > or = 1.5 and that with %Mag.30 < 40% was 83% and 73%, respectively. Our results indicate that the frequency-domain analysis of P waves in lateral leads is useful as is the time-domain analysis to detect patients with Paf. The AR20 > or = 1.5 and %Mag.30 < 40% provides accurate predictability of Paf.

Adult↗

Direct conversion of atrial flutter to sinus rhythm with low-output, short-duration transesophageal atrial pacing.

BACKGROUND AND HYPOTHESIS: Transesophageal atrial pacing (TAP) is useful for terminating paroxysmal non-self terminating atrial flutter (PAF); however, high output pacing of long stimulus duration causes severe symptoms such as chest pain. The objective of this study was to investigate the effect of low-output, short-duration TAP on the conversion of PAF. METHODS: We applied low-output (within 15 mA with a pulse duration of 10 ms), short-duration (within 4 s) TAP in 31 patients (50 +/- 19 years) with PAF. Transesophageal pacing was delivered with 10 pulses of burst pacing at intervals that were 20 ms shorter than those of the flutter wave length. When the conversion was unsuccessful, we delivered 20 pulses of burst pacing. RESULTS: Sixteen patients (52%) were converted directly to sinus rhythm and 12 (38%) to atrial fibrillation. Transesophageal pacing was ineffective in 3 (10%) patients. The duration of atrial flutter, maximum flutter wave amplitude, effective pacing intervals, underlying heart diseases, and cardiac function were not different between patients who had direct conversion to sinus rhythm and those converted to atrial fibrillation. The patients who had direct conversion to sinus rhythm had longer flutter wave cycle lengths than those converted to atrial fibrillation (248 vs. 221 ms, p < 0.005). No patient had complications and complained of any symptoms. CONCLUSION: Low-output, short-duration TAP was useful to convert PAF directly to sinus rhythm without side effects.

Adolescent↗