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Biomedical subjects

Kenichi Yamada

Publications and source records attributed to Kenichi Yamada.

23 records · Page 2Linked to original sources

Overhauser enhanced magnetic resonance imaging for tumor oximetry: coregistration of tumor anatomy and tissue oxygen concentration.

An efficient noninvasive method for in vivo imaging of tumor oxygenation by using a low-field magnetic resonance scanner and a paramagnetic contrast agent is described. The methodology is based on Overhauser enhanced magnetic resonance imaging (OMRI), a functional imaging technique. OMRI experiments were performed on tumor-bearing mice (squamous cell carcinoma) by i.v. administration of the contrast agent Oxo63 (a highly derivatized triarylmethyl radical) at nontoxic doses in the range of 2-7 mmol/kg either as a bolus or as a continuous infusion. Spatially resolved pO(2) (oxygen concentration) images from OMRI experiments of tumor-bearing mice exhibited heterogeneous oxygenation profiles and revealed regions of hypoxia in tumors (<10 mmHg; 1 mmHg = 133 Pa). Oxygenation of tumors was enhanced on carbogen (95% O(2)/5% CO(2)) inhalation. The pO(2) measurements from OMRI were found to be in agreement with those obtained by independent polarographic measurements using a pO(2) Eppendorf electrode. This work illustrates that anatomically coregistered pO(2) maps of tumors can be readily obtained by combining the good anatomical resolution of water proton-based MRI, and the superior pO(2) sensitivity of EPR. OMRI affords the opportunity to perform noninvasive and repeated pO(2) measurements of the same animal with useful spatial (approximately 1 mm) and temporal (2 min) resolution, making this method a powerful imaging modality for small animal research to understand tumor physiology and potentially for human applications.

Algorithms↗

Noninvasive imaging of tumor redox status and its modification by tissue glutathione levels.

Therapeutic regimens such as radiation or chemotherapy attempt to exploit the physiological differences between normal and malignant tissue. Tissue redox status and pO(2) are two factors that are hypothesized to be different in normal and malignant tissues. Methods that can detect subtle differences in the above physiological parameters would greatly aid in devising appropriate treatment strategies. We have previously used in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging techniques and shown that tumor tissues are highly reducing and hypoxic compared with normal tissues (P. Kuppusamy et al., Cancer Res., 58: 1562-1568, 1998). The purpose of the present study was to obtain spatially resolved redox data from normal and tumor tissues of radiation-induced fibrosarcoma (RIF-1) tumor-bearing mice and to examine the role of intracellular glutathione (GSH) on the tissue redox status. Experiments were performed using low-frequency (1.3 GHz) in vivo EPR spectroscopy and imaging techniques with a nitroxide redox probe. L-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH synthesis, was used to deplete tissue GSH levels. The results show the existence of significant heterogeneity of redox status in the tumor tissue compared with normal tissue. The tumor tissues show at least 4-fold higher concentrations of GSH levels compared with normal tissues in the tumor-bearing mice. Also BSO treatment showed a differential depletion of GSH and reducing equivalents in the tumor tissue. Thus, it appears that there is significant heterogeneity of tumor redox status and that manipulation of the tumor redox status may be important in tumor growth and therapy.

Animals↗

Single-point (constant-time) imaging in radiofrequency Fourier transform electron paramagnetic resonance.

This study describes the use of the single-point imaging (SPI) modality, also known as constant-time imaging (CTI), in radiofrequency (RF) Fourier transform (FT) electron paramagnetic resonance (EPR). The SPI technique, commonly used for high-resolution solid-state nuclear magnetic resonance (NMR) imaging, has been successfully applied to 2D and 3D RF-FT-EPR imaging of phantoms containing narrow-line EPR spin probes. The SPI scheme is essentially a phase-encoding technique that operates by acquiring a single data point in the free induction decay (FID) after a fixed delay (phase-encoding time), following the pulsed RF excitation, in the presence of static magnetic field gradients. Since the phase-encoding time remains constant for a given image data set, the spectral information is automatically deconvolved, providing well-resolved pure spatial images. Therefore, images obtained using SPI are artifact-free and the resolution is not significantly limited by the line width, compared to the images obtained using the conventional filtered back-projection (FBP) scheme, suggesting that the SPI modality may have advantages for EPR imaging of large objects. In this work the advantages and limitations of SPI as compared to FBP are investigated by imaging suitable phantom objects. Although SPI takes longer to perform than the FBP method, optimization of the data collection scheme may increase the temporal resolution, rendering this technique suitable for in vivo studies. Spectral information can also be extracted from a series of SPI images that are generated as a function of the delay from the excitation pulse.

Electron Spin Resonance Spectroscopy↗

Acutely exaggerated hepatitis B induced by the withdrawal of immunosuppressants in a seroconverted renal transplant recipient: report of a case.

The long-term reciprocal impact of renal transplantation on infection by hepatitis B virus (HBV) is still a matter of intense debate, and the topic remains controversial. We herein report the case of a 50-year-old male asymptomatic HBV carrier who had seroconverted to positive anti-HBe antibody (Ab) and received a kidney transplantation from a cadaver donor (HB surface(s) antigen (Ag)-negative). Nine months later, his kidney function deteriorated due to chronic rejection, and hemodialysis was temporarily required. Triple drug therapy (cyclosporine, prednisolone, azathioprine) for immunosuppression was changed to two-drug therapy (cyclosporine and prednisolone) at a reduced dosage because of this episode. After that episode, severe hepatitis with HBV antigenemia developed without any change in the serological state. The levels of DNA polymerase in a potential recipient from a cadaveric donor should be checked before transplantation to predict the occurrence of hepatitis when the recipient is an asymptomatic carrier of HBV, especially in cases of serologically HBeAg-negative, and anti-HBeAb-positive carriers.

Acute Disease↗

Left ventricular hypertrophy was infrequent in patients starting dialysis after undergoing a strict blood pressure control in the pre-dialytic period.

OBJECTIVE: We retrospectively investigated the factors influencing the left ventricular hypertrophy (LVH) occurrence in patients with chronic renal failure (CRF). METHODS AND PATIENTS: Blood pressure and echocardiographyically determined LVH were assessed in 110 patients on the basis of availability of monthly follow-up data obtained during the period of 2 years before the start of dialysis. When the patients showed the left ventricular mass index of not less than 125 g/m2, they were diagnosed as having LVH. Mean casual blood pressure distribution was classified into 5 groups: Group 1; <93 mmHg, Group 2; 93-100 mmHg, Group 3; 100-106 mmHg, Group 4; 106-114 mmHg and Group 5; >114 mmHg. RESULTS: LVH frequencies were 31.8, 72.7, 72.7, 81.8 and 95.5 (%) in Groups 1-5, respectively. Logistic regression showed that the factors influencing the progression of LVH were the duration of hypertension (per 1 year relative risk) (RR) 1.13, 95% confidential interval (CI) (1.01-1.26), treatment with angiotensin-converting enzyme inhibitors (ACE-1) (RR: 0.20, 95%CI: 0.04-0.99), pulse pressure (RR: 1.06, 95%CI: 1.00-1.11) and mean blood pressure (MBP). The RR of developing LVH increased progressively as MBP increased: Compared with LVH frequency in Group 1, RR of Group 2 was 4.38 (95%CI: 1.05-18.19), that of Group 3 was 5.50 (95%CI: 1.08-28.02), that of Group 4 was 5.66 (95%CI: 1.22-26.15), and that of Group 5 was 19.13 (95%CI: 1.75-209.4). CONCLUSION: Strict blood pressure control and ACE-I treatment could prevent LVH in patients with CRF.

Blood Pressure↗