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Biomedical subjects

Akira Tanaka

Publications and source records attributed to Akira Tanaka.

At least 73 records · Page 4Linked to original sources

PPAR(alpha) and PPAR(gamma) activators suppress the monocyte-macrophage apoB-48 receptor.

Certain triglyceride-rich lipoproteins (TRLs), specifically chylomicrons, dyslipemic VLDLs, and their remnants, are atherogenic and can induce monocyte-macrophage foam cell formation in vitro via the apolipoprotein B-48 receptor (apoB-48R). Human atherosclerotic lesion foam cells express the apoB-48R, as determined immunohistochemically, suggesting it can play a role in the conversion of macrophages into foam cells in vivo. The regulation of the apoB-48R in monocyte-macrophages is not fully understood, albeit previous studies indicated that cellular sterol levels and state of differentiation do not affect apoB-48R expression. Since peroxisome proliferator-activated receptors (PPARs) regulate some aspects of cellular lipid metabolism and may be protective in atherogenesis by up-regulation of liver X-activated receptor alpha and ATP-binding cassette transporter A1, we examined the regulation of apoB-48R by PPAR ligands in human monocyte-macrophages. Using real-time PCR, Northern, Western, and functional cellular lipid accumulation assays, we show that PPARalpha and PPARgamma activators significantly suppress the expression of apoB-48R mRNA in human THP-1 and blood-borne monocyte-macrophages. Moreover, PPAR activators inhibit the expression of the apoB-48R protein and, notably, the apoB-48R-mediated lipid accumulation of TRL by THP-1 monocytes in vitro. If PPAR activators also suppress the apoB-48R pathway in vivo, diminished apoB-48R-mediated monocyte-macrophage lipid accumulation may be yet another antiatherogenic effect of the action of PPAR ligands.

ATP Binding Cassette Transporter 1↗

Accumulation of 99mTc-PMT in renal metastasis of hepatocellular carcinoma.

We describe here a case in which 99mTc-Sn-N-pyridoxy-5-methyltryptophan (99mTc-PMT) scintigraphy was useful in diagnosing renal metastasis of hepatocellular carcinoma (HCC). A 62-year-old man who had undergone hepatectomy for HCC presented 6 years after initial diagnosis with left flank pain and was found on CT and MRI to have a tumor in the left kidney. Hepatobiliary scintigraphy using 99Tc-PMT was performed, and 99mTc-PMT accumulation was found in the tumor. Nephrectomy was performed and metastasis of HCC was confirmed.

Carcinoma, Hepatocellular↗

Can personality traits predict pathological responses to audiovisual stimulation?

The "Pockemon shock" is the most famous accident in the history of the broadcasting industry in Japan. Based on the experiences of this unfortunate accident from famous animation program "Pocket Monster", this study focused on the psychology and psychosomatics of the patients. A head-mounted display was used as the three-dimensional image presentation device and "Descent", a free software shooting game, was used as the software. Ten healthy adult male volunteers were used in this experiment after obtaining their informed consent. The oxygen metabolic change in the anterior lobe of the brain was measured by near infrared spectroscopy and recorded on an electrocardiogram. The mental scaling tendency of the object was analyzed using the type A behavior pattern and the hostility scaling. The Cook and Medley hostility (HO) scale from the Minnesota multiphasic personality inventory (MMPI) was also used in this experiment. From this scaling methodology, the paranoid scale, cynicism scale, lie scale, social support quality and social support quantity were calculated. All measured time series data were kept in the normal range, and no fatal arrhythmia or epilepsy were observed during experiments. In some cases, the brain oxygen metabolism may completely differ for the objects of Type A and Type B behavior patterns. On the whole, correlation did not become significant in type A scaling and hostility scaling. In a comparison of the percent changes of the HF in HRV with lie scaling, significant negative correlation was observed. The social support quantity was calculated from Cook and Medley, and significant negative correlations were observed with percent changes of LF/HF in HRV. The lie scale and social support quantity are opposite scaling. The sympathetic nervous system and parasympathetic nervous system have an opposite function also. Therefore, our results showed an interesting phenomenon, when considering the relationship between the autonomic function and the pathophysiological reaction to the audiovisual stimulations. As for the photo sensitive epilepsy, it was reported to be only 5-10% for all patients. Therefore, 90% or more of the cause could not be determined in patients who started a morbid response. The results in this study suggest that the autonomic function was connected to the mental tendency of the objects. By examining such directivity, it is expected that subjects, which show morbid reaction to an audiovisual stimulation, can be screened beforehand.

Acoustic Stimulation↗

Artificial myocardium with an artificial baroreflex system using nano technology.

Where is the place which should be helped in a patient with congestive heart failure? The answer may be contraction of the heart. At Tohoku University, development research of "the artificial myocardium" has been conducted, using a ball screw type electromagnetic motor. Furthermore, super-miniaturization is being attempted at present. Thus, a system with shape memory alloy is being developed. The cooling speed problem was solved by the application of the Peltier element. A drive at a speed equal to that of a heartbeat was realized by the application of this system. At present, a ventricular assist device is used for patients waiting for a heart transplant in Japan. An air driven type system disturbs a patient's QOL remarkably because it is connected to the drive device. With our concept, energy is provided by using the electromagnetic force from outside of the body by the use of transcutaneous energy transmission system. Magnetic shielding by amorphous fibers was used at Tohoku University to improve the total efficiency. A natural heart can alter the cardiac output corresponding to the demand. Artificial internal organs must participate in the system of the living body, too. Tohoku University has developed a resistance based artificial heart control algorithm, which simulated a baroreflex system to cope with every demand. Nano level sensing equipment is now under development at Tohoku University. At present, development is being conducted aiming at an "intelligent artificial myocardium".

Baroreflex↗

Myoglobin gene expression attenuates hepatic ischemia reperfusion injury.

BACKGROUND: Cellular functions are maintained by a continuous supply of ATP, which is supplied efficiently by mitochondrial oxidative phosphorylation. Since myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the liver, facilitates oxygen diffusion under low oxygen conditions and enhances oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated myoglobin expression. MATERIAL AND METHODS: After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the human myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for myoglobin, and cellular and hepatic ATP levels were examined. The effect of myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat. RESULTS: Myoglobin expression was confirmed in Hep3B and rat livers after AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h after AdCMVMyo transfection were significantly higher than control levels and those after adenovirus-mediated beta-galactosidase transfection. Finally, expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver. CONCLUSION: These results indicate that myoglobin gene transfer to the liver enhanced ATP levels both in vitro and in vivo and might be a novel strategy to reduce ischemia-reperfusion injury.

Adenosine Triphosphate↗

Effects of fibroblast growth inhibitor on proliferation and metastasis of oral squamous cell carcinoma.

Development of a new therapeutic approach to improve the prognosis of high grade invasion of oral squamous cell carcinoma is needed. To elucidate the effect of a fibroblast inhibitor (tranilast), we investigated the proliferation and metastasis of oral squamous cell carcinoma in a mouse model. The effect of tranilast on tumour growth, lymph node metastases, microvessel density, and the proliferating cell nuclear antigen (PCNA) labelling index of oral squamous cell carcinoma implanted into the tongue of nude mice was evaluated. Tumour growth and the incidence of cervical lymph node metastases were significantly suppressed by the administration of tranilast. The amount of fibrous tissue, the microvessel density, and the PCNA labelling index of tumour were also significantly reduced. Administration of a fibroblast inhibitor may well be clinically effective for the treatment of oral squamous cell carcinoma.

Animals↗

Binding site of novel 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine herbicides in the D1 protein of Photosystem II.

A series of replacement experiments of [(14)C]-triazines, [(14)C]-atrazine and [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine, bound to thylakoids isolated from wild-type and atrazine-resistant Chenopodium album (lambsquarters) were conducted. Replacement experiments of [(14)C]-triazines bound to wild-type Chenopodium thylakoids with non-labeled atrazine and 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine were carried out, to elucidate whether benzylamino-1,3,5-triazines use the same binding niche as atrazine. [(14)C]-Atrazine and [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine bound to wild-type thylakoids were replaced by non-labeled 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine and non-labeled atrazine, respectively. The above two replacements showed mutual competition. To clarify further whether benzylamino-1,3,5-triazines bind at the D1-protein to amino acid residue(s) different from atrazine or not, experiments to replace [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazines bound to atrazine-resistant Chenopodium thylakoids by non-labeled atrazine, 2-(4-bromobenzylamino)-4-methyl-6-trifluoromethyl-1,3,5-triazine, DCMU and DNOC were carried out. Although the bound [7-(14)C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine was difficult to be replaced even with high concentrations of atrazine, [(14)C]-labeled 1,3,5-triazine was competitively replaced by non-labeled 2-(4-bromobenzylamino)-4-methyl-6-trifluoromethyl-1,3,5-triazine, DCMU or DNOC. Thus, 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine herbicides are considered to bind to the same niche at the D1 protein as atrazine, but use amino acid residue(s) different from those involved with atrazine binding.

Journal Article↗

Application of the AMeX method to the evaluation of HER-2 status in breast carcinomas: comparison with the results of HercepTest.

The recent development of the recombinant humanized monoclonal antibody against HER-2 oncoprotein requires a simple and accurate method for the evaluation of HER-2 status in patients with breast cancers. We here report that the evaluation of the HER-2 status is improved by the use of the acetone-methanol-xylene (AMeX) method. Compared with an ordinary test of HercepTest, 25 out of 63 cases (39.7%) were scored upwards by the AMeX method. In addition, the HER-2 gene amplification was easily estimated by fluorescence in situ hybridization (FISH) using the AMeX method. Thus, the AMeX method is likely to provide more improved data about the HER-2 status in breast carcinoma specimens.

Breast Neoplasms↗

In vivo test of pressure head and flow rate estimation in a continuous-flow artificial heart.

To avoid using sensors with low biocompatibility and low durability in implantable total artificial heart (TAH) systems, the authors previously proposed a new method for estimating instantaneous values of flow rate and pressure head on the basis of voltage, current, and rotational speed in a motor driven centrifugal pump. The previous in vitro experiments showed that the proposed estimator could automatically compensate for the effect of the change in blood viscosity on the estimation accuracy by employing two kinds of autoregressive exogenous models. In this study, validity and reliability of this estimation method were ascertained in an acute animal experiment. In the experiment, two centrifugal blood pumps were implanted into an adult goat as a total artificial heart. Results of estimation were compared with true values when blood viscosity was changed by injecting physiological saline. The results indicated that the system could successfully estimate pressure head by compensating the change of viscosity, although the estimation accuracy of the in vivo estimation was not so high as that of the previous in vitro tests.

Animals↗

Recent progress in artificial organ research at Tohoku University.

Tohoku University has developed various artificial organs over the last 30 years. Pneumatic driven ventricular assist devices with a silicone ball valve have been designed by the flow visualization method, and clinical trials have been performed in Tohoku University Hospital. On the basis of these developments, a pneumatic driven total artificial heart has been developed and an animal experimental evaluation was conducted. The development of artificial organs in Tohoku University has now progressed to the totally implantable type using the transcutaneous energy transmission system with amorphous fibers for magnetic shielding. Examples of implantable systems include a vibrating flow pump for ventricular assist device, an artificial myocardium by the use of shape memory alloy with Peltier elements, and an artificial sphincter for patients with a stoma. An automatic control system for artificial organs had been developed for the ventricular assist devices including a rotary blood pump to avoid suction and to maintain left and right heart balance. Based upon the technology of automatic control algorithm, a new diagnostic tool for evaluating autonomic nerve function has been developed as a branch of artificial organ research and this new machine has been tested in Tohoku University Hospital. Tohoku University is following a variety of approaches aimed at innovation in artificial organs and medical engineering fields.

Academic Medical Centers↗

Chaos attractors of ventricular elastance to evaluate cardiac performance.

Quantitative evaluation of cardiac function is very important in the clinical application of a ventricular assist device. This article reports a new evaluating method of E max, which is the most reliable parameter to evaluate cardiac function. Fluctuation in the E max time series data was evaluated by the nonlinear mathematical analyzing method including chaos and fractal theory. Experimental goats were anesthetized with halothane inhalation, and left ventricular volume and pressure were measured with other hemodynamic parameters to evaluate E max during various drug administrations. E max was evaluated by two methods. One was the conventional pressure volume loop evaluation and the other was the parameter optimization method without left ventricular volume data. As a result, E max evaluated by the parameter optimization method correlated well with the E max with conventional PV curve. Furthermore, interesting results were obtained. There were rhythmical fluctuations in the E max time series data. By the methodology of Takens, E max time series data was embedded into the phase space and a strange attractor was observed. These results may be important when considering E max evaluation during left ventricular assistance.

Animals↗

Outflow control for avoiding atrial suction in a continuous flow total artificial heart.

Continuous flow blood pumps, such as axial flow and centrifugal pumps, have been gaining interest as circulatory devices for total artificial hearts (TAHs) because of their smaller size and simpler structure compared to pulsatile pumps. However, continuous flow pumps are more prone to atrial wall suction than pulsatile pumps are. Sudden increases in flow rate to meet changes in physiological demand, especially in the left pump, often cause atrial wall suction. In this study, a control algorithm to prevent atrial wall suction from occurring in the left atrium by controlling the rotational speed of the right pump, instead of reducing the cardiac output of the left pump, was developed and investigated. The method was tested in a mock circulatory system and in acute animal experiments with adult goats. Two centrifugal pumps were used to totally replace the circulatory function of the natural heart. The cardiac output of each pump was determined independently by a control algorithm running on a computer connected through a serial interface to the pump driving units. Results showed that left atrial wall suction could be prevented using this method, and that the method could be performed simultaneously with physiological control of the artificial heart.

Algorithms↗

Neuroendocrine tissue-specific transcription factor, BETA2/NeuroD, in gastric carcinomas: a comparison with chromogranin A and synaptophysin expressions.

BETA2/NeuroD (NeuroD) is a basic helix-loop-helix type of transcription factor mainly involved in neuroendocrine differentiation. In this study, we evaluated the prevalence of neuroendocrine differentiation in gastric carcinomas by analyzing the NeuroD expression in comparison with those of chromogranin A and synaptophysin. Of the 70 cases of gastric adenocarcinoma, the expressions of NeuroD, chromogranin A, and synaptophysin were detected in 17 (24.3%), four (5.7%), and 24 cases (34.3%), respectively, with preferential expressions in a non-solid type of poorly differentiated adenocarcinoma. The expression pattern of NeuroD was mostly concordant with that of synaptophysin and partly with chromogranin A, indicating that NeuroD serves as a good neuroendocrine marker in gastric adenocarcinomas. On the other hand, no immunoreactivity against NeuroD was detectable in nine cases of gastric neuroendocrine carcinomas, including small cell carcinomas, despite the presence of synaptophysin and chromogranin A expressions. These findings led us to conclude that neuroendocrine differentiation is estimated to be present in 20-30% of gastric adenocarcinomas with preference to a non-solid type of poorly differentiated adenocarcinoma. In addition, the negative expression of NeuroD in neuroendocrine carcinomas suggests that other regulatory mechanisms are possibly involved in the development of neuroendocrine carcinoma.

Adenocarcinoma↗

Improved cerebral perfusion after simultaneous stenting for tandem stenoses of the internal carotid artery--two case reports.

Two patients with extracranial internal carotid artery (ICA) stenosis and tandem stenosis of the ipsilateral intracranial ICA were treated simultaneously by angioplasty with stenting. A 68-year-old man who presented with neovascular glaucoma had 90% stenosis of the right cervical ICA and 80% stenosis of the ipsilateral petrous ICA. A 74-year-old man who suffered from transient ischemic attack had 75% stenosis of the left cervical ICA and 90% stenosis of the ipsilateral cavernous ICA. Hemodynamic compromise was confirmed in both patients. Tandem stenting of both extracranial and intracranial ICA stenoses was performed simultaneously in both patients without complications. Poststenting angiography demonstrated excellent dilation of both lesions and normalization of cerebral perfusion. Simultaneous tandem stenting for extracranial ICA stenosis with intracranial tandem stenosis is less invasive than open surgery in high-risk patients with hemodynamic compromise, especially if the major lesion responsible for cerebral hypoperfusion is difficult to determine.

Aged↗

Retrograde carotid stenting for isolated stenosis of the proximal common carotid artery--case report.

A 49-year-old female with a history of systemic hypertension and diabetes mellitus suffered transient right hemiparesis. Carotid angiography with arch-aortography detected severe stenosis of the proximal portion of the left common carotid artery. The left carotid bifurcation was surgically exposed and retrograde catheterization was performed to approach the proximal common carotid artery stenosis. The lesion was dilated with a balloon catheter and successfully stented without complications. The left internal carotid artery was clamped during the procedure to avoid embolism. Retrograde carotid stenting for stenosis of the proximal common carotid artery is a safe and effective alternative to conventional surgery in selected patients.

Angioplasty, Balloon↗

Resistant starches of beans reduce the serum cholesterol concentration in rats.

We examined the effects of the resistant starches of adzuki (Vigna angularis), kintoki (Phaseolus vulgaris, variety), and tebou (P. vulgaris, variety) beans on the lipid metabolism in rats. Rats were fed a cholesterol-free diet with 25 g of cornstarch (CS)/100 g diet, 25 g of adzuki starch (AS)/100 g diet, 25 g of kintoki starch (KS)/100 g diet, or 25 g of tebou starch (TS)/100 g diet for 4 wk. The cecal contents in the TS group were significantly higher than those in the CS and KS groups. There were no significant differences in body weight or food intake among the groups. The relative liver weight in the CS group was significantly greater than that of the AS, KS, and TS groups. The serum total cholesterol, VLDL+IDL+LDL-cholesterol, and triglyceride concentrations in the AS, KS, and TS groups were significantly lower than those in the CS group throughout the feeding period. Though the total hepatic cholesterol concentration in the TS group was significantly higher than that in the KS group, there were no significant differences between the CS and other starch groups. The cecal pH value in the CS group was significantly higher than that of the bean starch groups. The cecal butyric acid concentrations in the AS, KS, and TS groups were significantly higher than that in the CS group, and the cecal total short-chain fatty acid (SCFA) concentrations in the AS and TS groups were significantly higher than those of the CS group. The fecal cholesterol excretion of the AS, KS, and TS groups were significantly higher than that in the CS group. The fecal coprostanol excretion in the AS group was significantly higher than that in the CS group. There was a negative correlation between the serum VLDL+IDL+LDL-cholesterol concentration and fecal neutral steroid excretion (r = -0.664, p < 0.001) in the present experiment. Furthermore, the cecal total SCFA concentration was negatively correlated with the serum VLDL+IDL+LDL-cholesterol concentration (r = -0.665, p < 0.001) and positively correlated with fecal neutral steroid excretion (r = 0.481, p < 0.05). The cecal butyric acid level was also negatively correlated with the serum VLDL+IDL+LDL-cholesterol concentration (r = -0.609, p < 0.01) and positively correlated with fecal neutral steroid excretion (r = 0.658, p < 0.001). The results suggest that AS, KS, and TS elevate cecal SCFA concentration, in particular butyric acid concentration, and fecal neutral sterol excretion, and lower the serum total cholesterol level.

Animals↗

[A patient with advanced gastric cancer that response remarkably to combination chemotherapy of TS-1 and biweekly paclitaxel (TXL)].

We treated a patient with inoperable advanced gastric cancer and malignant ascites by combination chemotherapy of TS-1 and biweekly paclitaxel (TXL). After two courses the ascites had disappeared and the primary tumor was reduced. TS-1 (80 mg/body/day) was administered for 21 days followed by 7 days rest and TXL (100 mg/body) was administered on days 1 and 14 as one course. The patient could not eat at the time of hospitalization, but at the time of the second course he could eat a full serving of rice porridge. Grade 2 anemia and leukopenia were the only adverse reactions observed; no major adverse reactions were observed. These results suggest that with TS-1 and TXL combination chemotherapy, patients with advanced gastric cancer can achieve a marked improvement in quality of life.

Adenocarcinoma↗

Introduction of a Na+/H+ antiporter gene from Atriplex gmelini confers salt tolerance to rice.

We engineered a salt-sensitive rice cultivar (Oryza sativa cv. Kinuhikari) to express a vacuolar-type Na+/H+ antiporter gene from a halophytic plant, Atriplex gmelini (AgNHX1). The activity of the vacuolar-type Na+/H+ antiporter in the transgenic rice plants was eight-fold higher than that in wild-type rice plants. Salt tolerance assays followed by non-stress treatments showed that the transgenic plants overexpressing AgNHX1 could survive under conditions of 300 mM NaCl for 3 days while the wild-type rice plants could not. These results indicate that overexpression of the Na+/H+ antiporter gene in rice plants significantly improves their salt tolerance.

Caryophyllaceae↗