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Biomedical subjects

K Hirao

Publications and source records attributed to K Hirao.

At least 37 records · Page 2Linked to original sources

Association of synapse-associated protein 90/ postsynaptic density-95-associated protein (SAPAP) with neurofilaments.

BACKGROUND: Synapse-associated protein (SAP) 90/Postsynaptic density (PSD)-95-associated protein (SAPAP) (also called Guanylate kinase-associated protein/hDLG-associated protein) interacts with the guanylate kinase domains of PSD-95 and synaptic scaffolding molecule (S-SCAM) via the middle region containing 5 repeats of 14 amino acids. SAPAP also binds the recently identified proteins, nArgBP2 and synamon (also called Shank 1a), via the proline-rich region and the C-terminus, respectively. SAPAP is highly enriched in the Triton X-100-insoluble PSD fraction, and recruits PSD-95 into the Triton X-100-insoluble fraction in transfected cells. We have further characterized here the Triton X-100-insolubility of SAPAP and tried to identify the Triton X-100-insoluble structures which SAPAP interacts with. RESULTS: N-Methyl-D-aspartate receptors were recruited into the Triton X-100-insoluble fraction with PSD-95 by SAPAP. The N-terminal region of SAPAP was Triton X-100-insoluble, whereas the middle and C-terminal regions were Triton X-100-soluble. We identified proteins interacting with 35S-methionine-labelled SAPAP in the overlay assay, determined their amino acid sequences, and found them to be neurofilaments. SAPAP interacted with neurofilaments via the N-terminal region, was co-immunoprecipitated with neurofilaments from the rat brain, and co-localized with neurofilaments in transfected cells. CONCLUSION: SAPAP associates with neurofilaments via the N-terminal region and may link various components of the PSD to neurofilaments.

Actin Cytoskeleton↗

Changes in cerebral hemoglobin concentration and oxygen saturation immediately after birth in the human neonate using full-spectrum near infrared spectroscopy.

Using full-spectrum near infrared spectroscopy (fsNIRS), we measured changes in oxy- and deoxyhemoglobin (HbO2 and Hb), total hemoglobin (T-Hb) concentration, and hemoglobin oxygen saturation (SbO2) in the brain tissue of seven neonates immediately following birth. It was found that HbO2 rose rapidly within 2-3 min after birth. During the same time, there was a transient increase in T-Hb concentration, after which it decreased together with Hb. SbO2 increased rapidly after birth, from 18% at 1.5 min to about 55% at 5-6 min, followed by a gradual increase of about 10%. Oxygenation in the brain occurred much sooner in three subjects given oxygen for a short time immediately after birth than in those who did not receive oxygen. This preliminary study indicated that dynamic changes occur in cerebral circulation and oxygenation as part of the physiological changes taking place soon after birth.

Brain↗

Sensitive detection of myocardial contraction abnormality in chronic hemodialysis patients by ultrasonic tissue characterization with integrated backscatter.

Since acoustic properties of the myocardium are sensitive to the myocardial structure and the contractile conditions of myocyte, the authors evaluated cardiac dysfunction based on the integrated ultrasonic backscatter in 18 hemodialysis (HD) patients (duration: 102 +/- 84 months, mean age: 57.6 +/- 9.7 years) and 11 age-matched normals. The cyclic variation of integrated backscatter (CV-IB) at interventricular septum (IVS) and left ventricular posterior wall (PW) was measured and compared with percent fractional shortening (%FS) and percent wall thickening (%Th). The CV-IB of HD patients was smaller than that of control subjects (IVS: 6.2 +/- 1.1 dB vs 8.2 +/- 1.1 dB, p = 0.0003 and PW: 8.4 +/- 2.2 vs 10.3 +/- 1.3, p= 0.025). No significant difference was observed in %FS and %Th between HD patients and control subjects. In HD, the ratio of velocities of early diastolic inflow (E) to late atrial inflow was decreased (0.7 +/- 0.2 vs 1.1 +/- 0.7, p = 0.049) and deceleration time of E was prolonged significantly (200 +/- 28 msec vs 159 +/- 30 msec, p = 0.0082). In the absence of overt cardiac systolic dysfunction, myocardial damage indicated as a decrease in CV-IB and diastolic dysfunction identified on transmitral velocity waveform were detected, which may reflect from the myocardial fibrosis. As a mechanism, pressure overload, hyperparathyroidism, and anemia were neglected, and the other humoral factors may contribute to the myocardial damage in chronic renal failure.

Aged↗

Diagnostic significance of the morphological change in the atrial electrogram during Para-Hisian pacing.

Para-Hisian pacing (PHP), a pacing method to differentiate between conduction occurring over an accessory pathway (AP) from that over the atrioventricular node (AVN), is assessed essentially by comparing the timing in the atrial electrogams. Morphological change in the atrial electrograms is often observed during PHP, but its significance has not been investigated. Prior to the catheter ablation procedure, PHP was performed in 52 patients with an AP and in 36 patients with AV nodal reentrant tachycardia (AVNRT). The morphological change in the atrial electrograms, which was retrospectively assessed between the His bundle and proximal right bundle branch (HB-RB) captured and non-captured beats, was identified in 15 of 52 patients with an AP and in 26 of 36 patients with AVNRT. The atrial electrogram in the 6 of these 15 AP patients changed its morphology without overlapping the ventricular electrogram. All 6 AP patients exhibited a PHP pattern with the presence of 2 retrograde conduction routes, an AP and the AVN. In the patients demonstrating no morphological change in the atrial electrogram, 33 of 37 AP patients and all 10 AVNRT patients had only one retrograde conduction route. Morphological change in the atrial electrogram without overlapping the ventricular electrogram seems to have diagnostic significance indicating the presence of both AP and AVN conduction.

Adolescent↗

Evaluation of aberrant bile ducts before laparoscopic cholecystectomy: helical CT cholangiography versus MR cholangiography.

OBJECTIVE: The purpose of our study was to compare the accuracy of helical CT cholangiography and that of MR cholangiography in the diagnosis of aberrant bile ducts or cystic ducts before laparoscopic cholecystectomy. SUBJECTS AND METHODS: A total of 120 consecutive patients, including 114 patients with cholecystolithiasis and six with gallbladder polyps, were treated using laparoscopic cholecystectomy between November 1996 and August 1998. Eighteen (15%) of the 120 patients were suspected of having aberrant bile ducts or cystic ducts on helical CT cholangiography, and 16 of these 18 patients were subsequently examined on MR cholangiography. For the 16 patients who underwent both imaging examinations, findings from helical CT cholangiography and MR cholangiography were compared with intraoperative cholangiography. RESULTS: Aberrant bile ducts in 13 patients and aberrant cystic ducts in three patients were divided into six types on the basis of the results of intraoperative cholangiography. Although these types were clearly identified using helical CT cholangiography in all 16 patients, the anatomic variants were not correctly identified in seven (44%) of the 16 patients with MR cholangiography. False-negative findings were mainly a result of the insertion sites of the cystic ducts or aberrant bile ducts being obscured by aberrant bile ducts or duodenum. Two (2%) of the 120 patients developed mild adverse reactions to the contrast material, but neither required treatment. CONCLUSION: Helical CT cholangiography clearly showed aberrant bile ducts and cystic ducts, but visualization of these structures on MR cholangiography was unsatisfactory because of overlapping duodenum and hepatic ducts.

Adult↗

Comparisons of effects of raw and gelatinized sago and tapioca starches on serum and liver lipid concentrations in rats.

Effects of raw and gelatinized sago and tapioca starches on serum and liver lipid concentrations were compared in rats fed a cholesterol-enriched diet. Total serum cholesterol and the atherogenic index in the rats fed raw sago starch showed a statistically significant decrease and tendency to decrease, respectively, when compared with those of rats fed raw tapioca starch. Both the serum total cholesterol and atherogenic index in the rats fed gelatinized sago starch showed a tendency to decrease when compared with those of rats fed gelatinized tapioca starch. Serum triacylglycerol concentrations in the rats fed raw sago starch were significantly lower than those in the rats fed raw tapioca starch. The apparent digestibility of raw sago starch was lower than that of tapioca starch. The oval shapes of undigested raw sago starch granules collected from feces remained almost unchanged in shape, but had some holes and scrapes on their surfaces. The shape surfaces of undigested raw tapioca starch collapsed, thereby not retaining their original granule shapes. On the other hand, the amylose contents in the raw and gelatinized sago starches were higher than those in the raw and gelatinized tapioca starches. These results suggested that a decrease or a tendency to decrease in serum total cholesterol levels and atherogenic indexes in raw or gelatinized sago starch-fed rats compared to those of raw or gelatinized tapioca starch-fed rats, and a decrease in serum triacylglycerol concentrations in raw sago starch-fed rats compared to those of raw tapioca starch-fed rats, were due to the lower digestibility and higher amylose content of sago starch.

Amylases↗

[Seven cases of brain metastasis from papillary thyroid carcinoma].

Brain metastases from differentiated thyroid carcinoma are extremely rare and carry a poor prognosis. We describe here clinical details of 7 cases of brain metastases from papillary thyroid carcinoma. Of 153 patients with metastases from differentiated thyroid carcinoma (papillary in 123, follicular in 30) treated at our institution between 1981 and 1999, 7 patients (4.6%) had brain metastases. Histologically, the primary tumor was papillary carcinoma in all 7 cases. Four were males and 3 were females. The median age at first diagnosis of distant metastases was 63 yr (range, 47-76 yr). Of these patients, one had brain metastases only and six had metastases to the lungs as well. Five of these patients were treated with 131I. Three of these 5 patients had marked uptake in the metastases (131I positive) on post-therapy 131I scans and another 2 patients had no significant activity (131I negative) in both pulmonary and brain metastatic lesions. One of 3 patients with 131I positive lesions had intense activity in the brain tumor, but no uptake in multiple pulmonary metastatic tumors. In a patient with 131I positive brain metastases, the tumors progressed rapidly after 131I therapy. In another one patient, acute hemorrhage of the tumor occurred four days after 131I therapy, requiring surgical removal. Loner case of 131I negative 2 patients was treated with radiosurgery (gamma-knife) and complete reduction in tumor volume was observed. On the other hand, one of 2 patients receiving no 131I therapy had radiosurgery (x-knife) and remaining one received conventional external radiation and chemotherapy for small solitary brain and pulmonary metastatic tumors. These therapeutic interventions were useful in both cases. The mean length of survival after the development of brain metastases in the five patients who died of the disease was 30 months. One patient treated with x-knife has been alive at 21 months and another one who has 131I uptake in the brain tumor without uptake in lung lesions has been alive 15 months after diagnosis of brain metastasis. These results indicate that it is important to detect brain metastasis by imaging techniques and Tg measurements and give treatment as early as possible since the brain is the third most common distant metastatic site and the prognosis is poor.

Adolescent↗

Localization of membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 at tight junctions of epithelial cells.

Membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 and Synapse-associated protein (SAP) 97/human Discs-large tumor suppressor gene (hDLG) are ubiquitous isoforms of synaptic scaffolding molecule (S-SCAM) and Postsynaptic density (PSD)-95/SAP90, both of which are implicated in the structures of synapses, respectively. SAP97/hDLG is localized at epithelial junctions and may function as a scaffolding protein, but the subcellular localization or the function of MAGI-1/BAP1 has not been clarified. In intestinal epithelial cells, MAGI-1/BAP1 was localized at tight junctions, whereas SAP97/hDLG was localized diffusely at cell - cell junctions. In Madine Darby canine kidney (MDCK) cells, MAGI-1/BAP1 was colocalized with ZO-1, whereas SAP97/hDLG was colocalized with E-cadherin. In MDCK cells, dominant active and negative mutants of Rac1 small G protein changed the amounts of SAP97/hDLG at cell - cell junctions, but not that of MAGI-1/BAP1. When MDCK cells were switched to a low Ca2+ medium, E-cadherin disappeared from the plasma membrane, and cells were dissociated. The phorbol 12-myristate 13-acetate-treatment after the low Ca2+ switch induced a tight junction-like structure. MAGI-1/BAP1 was recruited with ZO-1 to this structure, but SAP97/hDLG or E-cadherin was not. These findings suggest that MAGI-1/BAP1 is a component of tight junctions of epithelial cells, and that its role is different from that of SAP97/hDLG.

Adaptor Proteins, Signal Transducing↗

Quantitative evaluation of left ventricular regional wall motion using a real-time wall thickness curve system with two-dimensional echocardiography.

The real-time wall thickness curve system was newly developed for recording left ventricular (LV) wall thickening (WT) on a 2-dimensional echocardiogram recorded in an arbitrary direction because of the scarcity of quantitative data on wall motion change during dobutamine-induced ischemia. This study tested the feasibility of this system for quantitative evaluation of wall motion. In normal subjects, accuracy and reproducibility of measurements were evaluated by comparison with measurements on a conventional M-mode echocardiogram and examination of inter- and intraobserver variability. In 28 patients with coronary artery disease, percent systolic wall thickening (%WT) was measured during dobutamine infusion in incremental doses of 6 microg/kg/min, from 6 to 30 microg/kg/min. Percent change in %WT by dobutamine was compared with percent coronary stenosis derived from quantitative coronary angiography. Analysis of the mean difference and 95% confidence intervals demonstrated good accuracy and reproducibility: 0.0 mm and intervals of -0.5 to 0.5 mm in diastolic wall thickening of LV posterior wall (PW) between both methods, -1% and -4% to 2% in %WT of IVS and LVPW between both observers, and -1% and -3% to 2% in that between both measurements. During dobutamine infusion, the percent change in %WT was significantly correlated with percent stenosis (r = 0.75, p<0.0001). The WT curve system enabled us to assess regional wall function as %WT and was available for quantitative observation of wall motion change during pharmacologic intervention. This system may reduce the effects of heart movement and may be of great clinical benefit in evaluating regional wall function.

Aged↗

Synamon, a novel neuronal protein interacting with synapse-associated protein 90/postsynaptic density-95-associated protein.

Guanylate kinase-associated protein (GKAP)/SAP90/PSD-95-associated protein (SAPAP)/DLG-associated protein (DAP) is a protein of the postsynaptic density (PSD), and binds to the guanylate kinase domain of PSD-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule. GKAP/SAPAP/DAP recruits PSD-95/SAP90 and its interacting protein, brain-enriched guanylate kinase-interacting protein, into the Triton X-100-insoluble fraction in transfected cells, suggesting that GKAP/SAPAP/DAP may link several PSD components to the Triton X-100-insoluble structures in the PSD. We have identified here a novel neuronal GKAP/SAPAP/DAP-binding protein and named it synamon. Synamon has seven ankyrin repeats at the NH(2) terminus followed by one src homology 3 domain and one PSD-95/Dlg-A/ZO-1 domain, and several proline-rich regions at the carboxyl terminus. Synamon interacts with the COOH-terminal region of GKAP/SAPAP/DAP via the middle region containing a PSD-95/Dlg-A/ZO-1 domain. Synamon was coimmunoprecipitated with SAPAP from rat crude synaptosomes and colocalized with SAPAP in primary cultured rat hippocampal neurons. Because synamon is composed of various protein-interacting modules, it may also interact with proteins other than GKAP/SAPAP/DAP to organize the architecture of the PSD.

Adaptor Proteins, Signal Transducing↗

Isolation and characterization of mammalian homologues of Caenorhabditis elegans lin-7: localization at cell-cell junctions.

In Caenorhabditis elegans, the vulval induction is mediated by the let-23 receptor tyrosine kinase (RTK)/ Ras signaling pathway. The precise localization of the let-23 RTK at the epithelial junctions is essential for the vulval induction, and requires three genes including lin-2, -7, and -10. The mammalian homologue of lin-2 has been identified as a protein interacting with a neuronal adhesion molecule, neurexin, and named CASK. CASK has recently been reported to interact with syndecans and an actin-binding protein, band 4.1, at epithelial and synaptic junctions, and to play central roles in the formation of cell-cell junctions. The product of C. elegans lin-7 directly interacts with let-23 RTK and localize it at epithelial junctions. Here, we report three rat homologues of lin-7 ubiquitously expressed in various tissues. These homologues are accumulated at the junctional complex region in cultured Madin-Darby canine kidney cells, and are also localized at the synaptic junctions in neurons. The mammalian homologues of lin-7 may be implicated in the formation of cell-cell junctions.

Amino Acid Sequence↗

MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting protein.

Postsynaptic density (PSD)-95/Synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are neuronal membrane-associated guanylate kinases. Because PSD-95/SAP90 and S-SCAM function as synaptic scaffolding proteins, identification of ligands for these proteins is important to elucidate the structure of synaptic junctions. Here, we report a novel protein interacting with the PDZ domains of PSD-95/SAP90 and S-SCAM and named it MAGUIN-1 (membrane-associated guanylate kinase-interacting protein-1). MAGUIN-1 has one sterile alpha motif, one PDZ, and one plekstrin homology domain. MAGUIN-1 is localized at the plasma membrane via the plekstrin homology domain and the C-terminal region and interacts with PSD-95/SAP90 and S-SCAM via a C-terminal PDZ domain-binding motif. MAGUIN-1 has a short isoform, MAGUIN-2, which lacks a PDZ domain-binding motif. MAGUINs are expressed in neurons and localized in the cell body and neurites and are coimmunoprecipitated with PSD-95/SAP90 and S-SCAM from rat crude synaptosome. MAGUIN-1 may play an important role with PSD-95/SAP90 and S-SCAM to assemble the components of synaptic junctions.

Adaptor Proteins, Signal Transducing↗

Interaction of S-SCAM with neural plakophilin-related Armadillo-repeat protein/delta-catenin.

Synaptic scaffolding molecule (S-SCAM) is a multiple PDZ domain-containing protein, which interacts with neuroligin, a cell adhesion molecule, and the NMDA receptor. In this study, we searched for S-SCAM-interacting proteins and obtained a neuralplakophilin-related armadillo-repeat protein (NPRAP)/delta-catenin. NPRAP/delta-catenin bound to the last PDZ domain of S-SCAM via its carboxyl-terminus in three different cell-free assay systems, was coimmunoprecipitated with S-SCAM from rat crude synaptosomes, and was localized at the excitatory synapses in rat hippocampal neurons. NPRAP/delta-catenin may be implicated in the molecular organization of synaptic junctions through the interaction with S-SCAM.

Adaptor Proteins, Signal Transducing↗

Effect of polyphenon-60 on the development of renal cell tumors in rats treated with N-ethyl-N hydroxyethylnitrosamine.

Green tea consumed as a beverage in Asia contains polyphenols, which contain about a 15% mixture of catechins. The present paper reports the effect of polyphenon-60 (60% pure catechin) on the development of renal cell neoplasms in Wistar rats pretreated with N-ethyl-N-hydroxyethylnitrosamine (EHEN): 0.1% polyphenon-60 in block diet was given over a period of 30 weeks while EHEN was given in drinking water for 2 weeks. The results appears to show a tendency for green tea catechins (GTC) to decrease the incidence of renal cell tumors greater than 3 mm in diameter in Wistar rats but not tumors that are less than 3 mm in diameter. Polyphenon-60 did not affect EHEN initiation in the kidneys of rats. It is postulated that free radicals induced by EHEN may be suppressed by GTC, resulting in a lowering of the tendency for tumor growth.

Animals↗

Intermittent bundle branch blocks in a patient with uncommon-type atrioventricular nodal reentrant tachycardia and enhanced atrioventricular nodal conduction.

We report on a patient with uncommon-type atrioventricular (AV) nodal reentrant tachycardia with a short tachycardia cycle length (235-270 ms), in whom transient wide QRS tachycardia with both left bundle branch block and right bundle branch block aberrancy were followed by narrow QRS complexes. In addition, His-ventricular (H-V) block and a sudden prolongation of the H-V interval occurred during the tachycardia. As the determinant of these unusual findings, the possibility that the anterograde limb of the reentry circuit has an enhanced AV nodal conduction property is discussed, as is the clinical significance of this type of tachycardia.

Adult↗

Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure.

The combination of ultrasound (US) exposure and ultrasound contrast agent (UCA) further increases the amount of drug-mediated thrombolysis. The aim of this study was to examine the efficacy of the combination of US and UCA on tissue plasminogen activator (tPA) thrombolysis, and the dependence on the microbubble structure. A catheter-type transducer capable of US emission (10 MHz, spatial peak temporal average intensity = 1.02 W/cm2 and peak negative pressure = 0.33 MPa) in the continuous-wave mode was employed. In 28 artificial white thrombi, serial changes in acoustic properties monitored by echography and histopathology during the tPA-mediated thrombolysis were analyzed. The thrombi were assorted to 4 groups; UCA nontreated (Control), sonicated albumin (A)-, SH-U508A (SH)- and dodecafluoropentane emulsion (DDFP)-treated groups. Persistence of microbubble opacification and thrombus weight were also measured. After the sample was suspended in a beaker with tPA (8000U) and 100 mL of saline, the UCA was administered and the mixture exposed to US for 10 min. Weight reduction of the thrombus was greatest in the DDFP Group (-49 +/- 8%), and that in the A Group (-8 +/- 5%) was not significantly different from that in the Control Group (-5 +/- 1%). The persistence of the microbubbles expressed as the decay of the time-intensity curve, was longest in the DDFP Group. The echo intensity of the superficial layer of the thrombus exposed to US was high and weight loss was marked. Multiple cavity formation was observed histopathologically. The stability of the microbubbles was an important factor of the US and UCA enhancement effect on tPA-mediated thrombolysis. This combination therapy has potential for clinical application in patients with thrombotic arterial and venous occlusion and left arterial thrombus.

Adult↗

The response of the slow atrioventricular nodal pathway to temperature.

The present study attempted to determine the lowest temperature at which the slow atrioventricular nodal pathway responds to heating and the temperature necessary for successful ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). The study group comprised 23 consecutive patients (14 women, 9 men) with symptomatic AVNRT. Radiofrequency current was delivered at the slow pathway potential recording site using a HAT 200S catheter ablation system. Successful radiofrequency ablation of the slow pathway was achieved in all 23 patients. Junctional beats, suggesting the response of the slow pathway to temperature, were detected in 62 of the total 136 applications. The temperature measured at the first junctional beat was 45.4+/-4.2 degrees C. The maximum temperature required for the successful ablation of AVNRT ranged from 45 to 88 degrees C. There were no complications except for 1 patient with transient atrioventricular (AV) block. There were no recurrences of AVNRT during follow-up. The lowest temperature at which the slow pathway was responsive to heat was quite similar to that for accessory pathways or the AV junction. However, the temperature required for the successful ablation of AVNRT differed markedly among the patients.

Adult↗