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Biomedical subjects

Takashi Hamada

Publications and source records attributed to Takashi Hamada.

14 recordsLinked to original sources

Primary liposarcoma of gallbladder diagnosed by preoperative imagings: a case report and review of literature.

A 49-year-old Japanese woman was referred to our department because of high fever and a huge abdominal mass. Computed tomography (CT) and magnetic resonance (MR) imagings revealed a tumor, about 30 cm in diameter,occupied the right hepatic lobe and the peritoneal cavity. Abdominal angiography showed that the tumor was fed mainly by the cystic artery. We preoperatively diagnosed angiosarcoma of the gallbladder and performed tumor resection with cholecystectomy because the tumor was almost capsulated,however the posterior wall of the gallbladder attached to the tumor firmly. Histologically,the tumor was composed of spindle cells including lipoblasts with cellular pleomorphism, which were also detected in the muscular layer of the gallbladder. We finally diagnosed pleomorphic liposarcoma of the gallbladder. At 10 mo and 29 mo after the first operation, she underwent two more operations because of recurrence. Now she has a good quality of life 3 yr and 6 mo after the first operation.

Angiography↗

A model for the mechanism of generating the auditory evoked field.

The auditory evoked potentials and fields, recorded with electro- and magneto-encephalography, respectively, have the prominent peak at the latency of about 100 ms, named N100(m). The mechanism for generating the peak is not yet fully elucidated, however. Firstly, this study reviewed empirical results on the mechanism that had been previously published by the same author. The results showed that phases of the ongoing oscillations at around 6 Hz above the auditory cortex are locked with respect to onsets of the auditory stimuli during the period of N100 m, and also that powers of the oscillations are increased during the same period. Taking into account these results as well as another evidence that the peak arises from multiple sources within the auditory cortex, a model for the mechanism of generating the auditory N100 m was proposed. The model assumed several oscillators in the auditory cortex, whose phases were locked during the period of N100 m, but not locked at other periods. Computer simulation validated the model. The model could represent a starting point for further experiment and simulation.

Acoustic Stimulation↗

Design and synthesis of highly active Alzheimer's beta-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability.

Recently, we reported potent and small-sized BACE1 inhibitors KMI-358 and KMI-370 in which the Glu residue is replaced by a beta-N-oxalyl-DAP (l-alpha,beta-diaminopropionyl) residue at the P(4) position. The beta-N-oxalyl-DAP group is important for enhancing BACE1 inhibitory activity, but these inhibitors isomerized to alpha-N-oxalyl-DAP derivatives in solvents. Hence, we used a tetrazole moiety as a bioisostere of the free carboxylic acid of the oxalyl group. KMI-420 and KMI-429, containing a tetrazole ring, showed improved stability and potent enzyme inhibitory activity.

Amyloid Precursor Protein Secretases↗

Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation.

Several reports claim that portal hypertension after living-donor liver transplantation (LDLT) adversely affects graft function, but few have assessed the impact of portal venous pressure (PVP) on graft regeneration. We divided 32 adult LDLT recipients based on mean PVP during the 1st 3 days after LDLT into a group with a PVP > or = 20 mm of Hg (H Group; n = 17), and a group with a PVP < 20 mm of Hg (L Group; n = 15). Outcome in the H Group was poorer than in the L Group (58.8 vs. 92.9% at 1 year). Peak peripheral hepatocyte growth factor (HGF) during the 1st 2 weeks was higher in the H Group (L: 1,730 pg/mL, H: 3,696 pg/mL; P < .01), whereas peak portal vascular endothelial growth factor (VEGF) level during the 1st week was higher in the L Group (L: 433 pg/mL, H: 92 pg/mL; P < .05). Graft volume (GV) / standard liver volume (SLV) was higher in the H Group (L / H, at 2, 3, and 4 weeks, and at 3 months: 1.02 / 1.24, .916 / 1.16, .98 / 1.27, and .94 / 1.29, respectively; P < .05). Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume. In conclusion, early postoperative PVP elevation to 20 mm of Hg or more was associated with rapid graft hypertrophy, higher peripheral blood HGF levels, and lower portal VEGF levels; and with a poor outcome, graft dysfunction with hyperbilirubinemia, coagulopathy, and severe ascites. Adequate liver regeneration requires an adequate increase in portal venous pressure and flow reflected by clearance of HGF and elevated VEGF levels.

Adult↗

Portable type signal-averaged electrocardiography with dipyridamole: a new and convenient method to detect patients with coronary artery disease and ischemia.

BACKGROUND: Whether or not patients with coronary artery disease (CAD) could be easily detected at the bedside using dipyridamole stress was investigated using a portable type signal-averaged electrocardiography (portable SAECG). METHODS AND RESULTS: The standard 12-lead QRS wave SAECG was performed at the bedside before and after dipyridamole stress in 30 patients with angiographically significant stenotic lesions, who had positive myocardial ischemia in the dipyridamole-thallium myocardial perfusion imaging (CAD group), and 33 patients with no significant stenotic lesions, who had negative imaging (control group). The filtered QRS duration (fQRSd) before and after dipyridamole stress was determined by the vector magnitude method and the difference (DeltafQRSd) was obtained. Furthermore, the DeltafQRSd was obtained using the multiphasic oscillation method, as well at the same standard 12-lead, and the maximal value of changes in fQRSd (MAX DeltafQRSd) between the 12 leads was determined. The DeltafQRSd was similar between 2 groups (p = 0.11). The MAX DeltafQRSd associated was significantly greater in the CAD group (p < 0.0001). When a cut-off value of MAX DeltafQRSd > or = 5 ms was used for the detection of CAD, the sensitivity and specificity were 97 and 94%, respectively. CONCLUSION: The portable dipyridamole-stress SAECG easily detect CAD and myocardial ischemia at the bedside.

Aged↗

A neuromagnetic analysis of the mechanism for generating auditory evoked fields.

Averaged and non-averaged neuromagnetic responses to repetitive transients of sound were analyzed in the frequency and time domains. It was found that ongoing oscillations between 3 and 16 Hz are relevant to the generation of auditory evoked fields (AEF). First, phases of the oscillation were locked at around the timings of N100m, but randomly distributed from trial to trial at the other timings. Secondly, amplitudes of the oscillation were larger on average at around the timings of N100m than at the other timings, although the amplitudes fluctuated from trial to trial with almost the same standard deviations throughout the periods of observation. Thirdly, spatial distributions of the oscillatory activities were often reduced to an equivalent current dipole in the auditory cortex at around the timings of N100m, but seldom reduced at the other timings. An explanation of these results would be to suppose several oscillators within the cortex whose phases are locked at around the timings of N100m, but fluctuated randomly at the other timings.

Acoustic Stimulation↗

Laparoscopic spleen-preserving pancreatic tail resection for an intrapancreatic accessory spleen mimicking a nonfunctioning endocrine tumor: report of a case.

Laparoscopic surgery is now performed for several pancreatic disorders, such as benign tumors of the pancreatic body or tail, which are a good indication for laparoscopic resection. However, the risk of pancreatic fistula after distal pancreatectomy, performed laparoscopically or by open surgery, is a topic of debate. We report the case of a 61-year-old man in whom a routine follow-up computed tomography (CT) scan showed a solid, well-defined mass, 1.5 cm in diameter, in the pancreatic tail. The mass was homogeneously enhanced from the early phase to the super-delayed phase on enhanced CT. We suspected a nonfunctioning endocrine tumor of the pancreas, and surgery was performed laparoscopically. After dissecting the pancreatic tail away from the splenic hilum and the splenic vessels, it was resected using only a linear stapler. The histological diagnosis was an intrapancreatic accessory spleen. The patient was discharged on postoperative day 14, but was readmitted 6 days later because of a pancreatic fistula, which was treated by CT-guided percutaneous drainage.

Choristoma↗

Speech offsets activate the right parietal cortex.

Speech offsets, i.e., sudden transitions from continuous speech sound to silence, activated both hemispheres differently. In addition to peak activities in the bilateral temporal cortices at about 120 ms after the offsets, the right parietal cortex was activated later irrespective of the stimulated ear. The result was discussed in the context of auditory attention.

Adult↗

KMI-008, a novel beta-secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-state mimic: design and synthesis of substrate-based octapeptides.

A novel class of substrate-based beta-secretase (BACE1) inhibitors containing a hydroxymethylcarbonyl (HMC) isostere was designed and synthesized. Phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] was an effective transition-state mimic at the P(1) position. Structure-activity relationships (SARs) of the P(3)-P(3)' positions of BACE1 inhibitors were studied.

Amino Acid Sequence↗

Antibiotic cyclic AMP signaling by "primed" leukocytes confers anti-inflammatory cytoprotection.

The mechanism underlying anti-inflammatory effects of macrolide antibiotics remains uncertain. In this study, we first show the evidences concerning the possible link between leukocytic cyclic adenosine monophosphate (cAMP) signaling and the mechanism of anti-inflammatory, cytoprotective actions of macrolides. The clinical range of macrolides (i.e., erythromycin, roxithromycin, and clarithromycin) preferentially inhibited nuclear factor-kappaB activation mediated by reactive oxygen intermediates, inducing cAMP-dependent signaling [i.e., cAMP and cAMP-responsive element-binding protein (CREB)] by "primed" but not "resting" leukocytes. In this context, cAMP/CREB inhibition with adenosine 3':5'-cyclic monophosphothioate, rp-isomer (rp-cAMPs) and CREB decoy oligonucleotides reduced the anti-inflammatory actions of macrolides. These results thus indicate that macrolide-induced cAMP/CREB signaling, selectively by primed leukocytes, plays a major role in the mechanism of anti-inflammatory actions of macrolides.

Animals↗

Mechanisms for atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

INTRODUCTION: Paroxysmal atrial fibrillation (PAF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. To elucidate the mechanisms for PAF, we performed electrophysiologic studies (EPS) before and after ablation of accessory pathways (APs). METHODS AND RESULTS: We investigated 24 patients with WPW syndrome who had AV reciprocating tachycardia and prior PAF and had undergone successful ablation of APs. Patients in whom atrial fibrillation (AF) was induced by EPS at day 7 after ablation were considered the inducible AF group (n = 14), and patients in whom AF was not induced by EPS at day 7 after ablation were considered the noninducible AF group (n = 10). Fifteen patients with AV nodal reentrant tachycardia (AVNRT) but without PAF who underwent ablation of the slow AV nodal pathways served as the control group (AVNRT group). Maximal atrial conduction delay and conduction delay zone, which are indices of atrial vulnerability, were measured before and after ablation. Before ablation, maximal atrial conduction delay and conduction delay zone were significantly greater (P < 0.0001 and P < 0.0001, respectively) in the two WPW syndrome groups than in the AVNRT group, indicating increased atrial vulnerability in WPW syndrome with PAF. After ablation, these parameters did not change in the inducible AF group, whereas they were significantly (P < 0.0001) decreased in the noninducible AF group and were not different from those in the AVNRT group, indicating normalized atrial vulnerability in the noninducible AF group after ablation. The prospective study demonstrated that PAF recurred only in the inducible AF group during long-term follow-up (17+/-7 months). CONCLUSION: The findings of this study suggest that there are two mechanisms of PAF in patients with WPW syndrome: one mechanism is reversible and AP-dependent atrial vulnerability, and the other is intrinsic and AP-independent atrial vulnerability.

Adolescent↗

P wave signal-averaged electrocardiography predicts recurrence of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome who underwent successful catheter ablation: a prospective study.

INTRODUCTION: Paroxysmal atrial fibrillation (PAF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Catheter ablation of the accessory pathway eliminates PAF in some patients, but PAF frequently recurs in other patients. The present study was designed to determine prospectively whether P wave signal-averaged electrocardiography (P-SAECG) predicts the recurrence of PAF after successful ablation in patients with WPW syndrome. METHODS AND RESULTS: Forty-six patients with WPW syndrome who had episodes of PAF were prospectively followed. SAECG recording was performed on day 7 after successful ablation of the accessory pathway at study entry. Abnormal P-SAECG for the prediction of recurrence of PAF was defined as a filtered P wave duration > 130 msec. Eleven patients had an abnormal P-SAECG (group 1), whereas 35 patients (group 2) did not. The two groups did not differ in terms of gender, age, left atrial dimension, and atrial vulnerability as determined by electrophysiologic study. During follow-up (40 +/- 19 months), the recurrence of PAF was noted in 10 (91%) of 11 patients in group 1, whereas it was observed in only 2 (6%) of 35 patients in group 2. Kaplan-Meier analysis revealed that the recurrence of PAF was significantly more frequent in group 1 than in group 2 (log rank test, P < 0.0001). By multivariate analysis, filtered P wave duration >130 msec was an independent predictor of recurrence of PAF after ablation (Chi-square = 21.5, P < 0.0001). CONCLUSION: The results of this study indicate that P-SAECG may be useful for identifying patients at risk for recurrence of PAF after successful ablation of WPW syndrome.

Adolescent↗