PubMed HealthSearch

Biomedical subjects

S Watanuki

Publications and source records attributed to S Watanuki.

At least 19 recordsLinked to original sources

Differential gene transcriptional regulation of Gi isoforms and Gs protein expression in diabetic rat hearts.

Many cardiac diseases can be associated with alterations in the function and quantity of G proteins. We examined the gene expressions and protein levels of Gi-1alpha, Gi-2alpha, Gi-3alpha and G(s alpha) in ventricular myocardial preparations from rats 4-6 weeks after induction of diabetes with streptozotocin in comparison with those from age-matched control rats. Diabetic rat myocardium exhibited reductions in the protein levels of Gi-2alpha and Gi-3alpha by 22+/-2% and 57+/-2%, respectively. In diabetes, 22% and 53% reductions in myocardial mRNA levels of Gi-2alpha and Gi-3alpha were observed. Although a faint protein signal of Gi-1alpha was detectable, no apparent expression of mRNA for Gi-1alpha was found in either control or diabetic myocardium. The reduced protein and mRNA levels of Gi-2alpha and Gi-3alpha were prevented by insulin therapy. No change was found in the protein and mRNA levels of G(s alpha) in diabetic myocardium. In conclusion, diabetes leads to a differential regulation of protein expressions of G(i alpha) isoforms and G(s alpha) in ventricular myocardium. The reduced expression of Gi-2alpha and Gi-3alpha proteins can be explained, at least in part, by the decreases in the transcriptional levels.

Animals

Predominant contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats: association with an increased level of G(qalpha) expression.

The purpose of this study was to determine the mechanism responsible for alterations in NaF-induced contractions of blood vessels from streptozotocin-induced diabetic rats. In the presence of AlCl(3), NaF (>/=7.5 mM) produced significantly greater contractions in diabetic aorta and mesenteric artery compared with age-matched controls. Pretreatment with 1 microM nifedipine eliminated the enhanced contractile responses of diabetic vessels to NaF, resulting in no difference in the magnitude of NaF-induced contractions between control and diabetic vessels. In the presence of 100 microM deferoxamine, an Al(3+) chelator, NaF-induced contractions of diabetic vessels were markedly attenuated, whereas only the responses to lower concentrations of NaF were reduced in control vessels. No significant difference was found in the peak amplitude of transient contractions induced by 10 microM cyclopiazonic acid between control and diabetic vessels. The addition of 10 microM okadaic acid produced attenuated contractions in diabetic vessels. These findings indicate no involvement of the inhibitory effects of NaF on endoplasmic reticular Ca(2+)-pump ATPase and protein phosphatases in the genesis of the enhanced responsiveness of diabetic vessels to NaF. Western blot analysis showed a 2.5-fold increase in the expression of G(qalpha) in diabetic aortic membranes. In contrast, the G(ialpha) level was modestly decreased and the G(salpha) and G(betagamma) levels were unchanged in diabetes. The present results suggest that enhanced vascular contractions to NaF in diabetes is attributed predominantly to a G protein-mediated Ca(2+) channel activation that results from markedly increased G(qalpha) expression in vascular tissues under this pathological state.

Aluminum Chloride

Easy detection of tumor in oncologic whole-body PET by projection reconstruction images with maximum intensity projection algorithm.

Whole-body PET scanning for an oncology study produces a large number of transaxial images by data acquisition over multiple bed positions. The sagittal and coronal reformatted images are often used for better understanding of radioisotope distribution. We reduced the number of PET images by calculating projection images and evaluated the merit of additional data processing for the visualization and detection of tumors. After reconstructing whole-body 18F-FDG PET images (6-8 bed positions) of eight cancer patients, antero-posterior and lateral projection images were calculated by the maximum intensity projection (MIP) algorithm, the standard deviation projection (SD) algorithm and the summed voxel projection (SUM) algorithm. The projection images were compared with 2D whole-body images for visualizing foci. The focal uptakes of various positions in original whole-body PET data (294-392 transaxial images) were visualized on only two MIP reformatted images when superimposition of hot spots did not occur. Even if one hot spot was superimposed over the other hot spot, we could recognize the existence of at least one focus and determine the true positions of the hot spots from corresponding transaxial images. The SD image was found inferior for showing a contrast of small foci to the corresponding MIP images in the neck, mediastinum and abdomen. The SUM image failed to visualize many metastatic lesions. MIP is a promising technique for the easy preliminary assessment of tumor distribution in oncologic whole-body PET study.

Algorithms

18F-FDG PET imaging of muscle activity in runners.

UNLABELLED: PET with three-dimensional data acquisition using 18F-fluorodeoxyglucose (FDG) was applied to evaluate skeletal muscle activity in runners. METHODS: Seven healthy adult male volunteers were studied. They ran for a total of 35 min, 15 min before and 20 min after intravenous injection of FDG. Another 7 adult male control subjects were also examined at rest. Images obtained through a set of whole-body PET scans were analyzed. Regions of interest (ROIs) were manually drawn on images of muscles of both thighs, legs and feet, and the standardized uptake ratio (SUR) and total radioactivity distribution (TRD) for each region were calculated. RESULTS: The work load was below the anaerobic threshold. SUR of foot, leg and thigh were low at rest but during running increased 5.19, 4.30 and 1.74 times, respectively. The SUR of posterior-to- anterior compartment of the leg was 1.1+/-0.1 at rest and 1.6+/-0.5 (P < 0.01) during running. The laterality index of both SUR and TRD changed significantly only in the foot of the dominant side during running. TRD of the leg, less than half that of the thigh at rest, became equivalent to that of the thigh during running. TRD of the foot did not change significantly. CONCLUSION: Sole muscles showed highest metabolic activation per unit volume during running, which was higher in the dominant side. Comparison of whole muscle activity during running indicated the highest metabolic activation was in the posterior compartment of the leg, whereas thigh muscles showed relatively little changes during running. Our data indicate that whole-body FDG PET, especially three-dimensional data acquisition, is a useful tool for the investigation of muscular activity during exercise.

Adult

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of 18FDG, three-dimensional positron emission tomography and rectilinear scan.

We tried to simultaneously obtain the elimination constant of mucociliary clearance and the pulmonary epithelial permeability constant after inhalation of 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) solution by carrying out whole lung positron emission tomography and a rectilinear scan in rabbit experiments. The elimination constant of pulmonary epithelial permeability was obtained from the decrease in the amount of the radioactivity with time in the region of interest (ROI) confined to the lungs, trachea and tracheal cannula in the rectilinear scan. The total elimination constant of the radioactivity in the lungs was obtained from the ROI confined to the lungs in the tomography. The mucociliary clearance rate constant in the lungs was then obtained after subtracting the elimination constant of the pulmonary epithelial permeability from the total elimination constant of the 18FDG in the lungs. The mucociliary clearance constant in the trachea was calculated from the residual radioactivity in the trachea and the mucociliary clearance constant in the lungs. The mean pulmonary epithelial permeability constant was 0.0020% min(-1) obtained from the rectilinear scan. The mean mucociliary clearance constants of the lungs and the trachea were 0.0006 and 0.025% min(-1), respectively. These results indicated that the pulmonary epithelial permeability and mucociliary clearance could be evaluated simultaneously with 18FDG by using three-dimensional positron emission tomography and a rectilinear scan.

Administration, Inhalation

Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-D-glucose using whole-body positron emission tomography and magnetic resonance imaging.

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-D-glucose (18F-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for 18F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the "Japanese reference man" to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1x10(-1), 3.7x10(-2) and 2.8x10(-2) mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9x10(-2) mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1x10(-2) mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered 18F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals.

Adult

Estimation of internal absorbed dose of L-[methyl-11C]methionine using whole-body positron emission tomography.

L-[Methyl-11C]-methionine (11C-methionine) is proposed as a useful radiotracer for tumour diagnosis. Human biodistribution data of cumulated activities and absorbed doses estimated by the MIRD (medical internal radiation dosimetry) method for 11C-methionine are not available in the literature. In this study we measured the organ activity for 11C-methionine by using whole-body positron emission tomography (PET) and estimated the absorbed doses to 25 organs by the MIRD method. Whole-body dynamic PET scans were performed on five normal volunteers to measure the time course of the organ activity concentration (activity/volume) after intravenous administration of 11C-methionine. Cumulated activities of the ten source organs were calculated from the time-activity curves, obtained from the dynamic PET data. Absorbed dose estimates were performed by the MIRD method for the Caucasian reference man and for the Japanese reference man. The organs which received the highest absorbed doses for the Caucasian reference man were found to be the bladder wall (2.7x10(-2) mGy/MBq), the pancreas (1.9x10(-2) mGy/ MBq), the liver (1.8x10(-2) mGy/MBq) and the kidney (1.1x10(-2) mGy/MBq). The effective doses for the Caucasian reference man and the Japanese reference man were calculated as 5.2x10(-3) and 5.0x10(-3) mSv/MBq, respectively.

Adult

Novel 5-hydroxytryptamine 4 (5-HT4) receptor agonists. Synthesis and gastroprokinetic activity of 4-amino-N-[2-(1-aminocycloalkan-1-yl)ethyl]-5-chloro-2-methoxybenzamide s.

A novel series of 4-amino-N-[2-(1-aminocycloalkan-1-yl)ethyl]-5-chloro-2-methoxyb enzamides. derivatives (1), which had amines conformationally restricted due to the effect of repulsion by neighboring substituents, were prepared and evaluated for 5-hydroxytryptamine 4 (5-HT4) agonistic activities by using the contraction of longitudinal muscle myenteric plexus (LMMP) of guinea pig ileum. One of the most potent compounds in this series was 4-amino-5-chloro-N-[2-(1-dimethylamino-1-cyclohexyl)ethyl]-2-methoxybenz amide (1c, YM-47813) with an EC50 value of 1.0 microM on LMMP. This compound effectively enhanced gastric motility and gastric emptying in conscious dogs by oral administration (1-3 mg/kg).

Animals

Performance evaluation of a large axial field-of-view PET scanner: SET-2400W.

The SET-2400W is a newly designed whole-body PET scanner with a large axial field of view (20 cm). Its physical performance was investigated and evaluated. The scanner consists of four rings of 112 BGO detector units (22.8 mm in-plane x 50 mm axial x 30 mm depth). Each detector unit has a 6 (in-plane) x 8 (axial) matrix of BGO crystals coupled to two dual photomultiplier tubes. They are arranged in 32 rings giving 63 two-dimensional image planes. Sensitivity for a 20-cm cylindrical phantom was 6.1 kcps/kBq/ml (224 kcps/microCi/ml) in the 2D clinical mode, and to 48.6 kcps/kBq/ml (1.8 Mcps/microCi/ml) in the 3D mode after scatter correction. In-plane spatial resolution was 3.9 mm FWHM at the center of the field-of-view, and 4.4 mm FWHM tangentially, and 5.4 mm FWHM radially at 100 mm from the center. Average axial resolution was 4.5 mm FWHM at the center and 5.8 mm FWHM at a radial position 100 mm from the center. Average scatter fraction was 8% for the 2D mode and 40% for the 3D mode. The maximum count rate was 230 kcps in the 2D mode and 350 kcps in the 3D mode. Clinical images demonstrate the utility of an enlarged axial field-of-view scanner in brain study and whole-body PET imaging.

Bone Neoplasms

Effects of reduction in arousal level caused by long-lasting task on CNV.

The present study aimed at investigating an inverted-U relationship between contingent negative variation (CNV) and arousal level by examining the effects on CNV of gradually reduced arousal level by long-lasting task. The subjects conducted a simple reaction time task consisting of warning stimuli (S1) and imperative stimuli (S2). This task consisted of 200 trials and lasted about 40 minutes. During this task, spontaneous EEG before S1 and SPL (skin potential level) were measured as indicators for arousal level. The 200 CNV, EEG and SPL data were classified into 5 blocks each of which included 40 trials of data. Analysis was made in seven subjects in whom reduction in the arousal level in long-lasting task was shown by increase in the relative power values of alpha waves before S1 and decrease in the SPL. As a result, the amplitude of early CNV at Fz was observed to increase from the earlier half phase (block 1) to the middle phase (block 3) and to decrease from the middle phase (block 3) to the latter half (block 5). In the middle phase, the amplitude was the greatest. The low amplitude of early CNV in the early half of the task (block 1) was inferred to have been induced by excessive arousal state because of the low relative power values of alpha waves and the high SPL at this time. On the other hand, the low amplitude in the later phase (block 5) was inferred to have been induced by reduction in arousal level because of the high relative power values of alpha waves and the low SPL. These results suggested that CNV amplitude and arousal level was in an inverted-U relationship.

Adult

Effects of changes in arousal level by continuous light stimulus on contingent negative variation (CNV).

The purpose of the present study was to investigate an inverted-U relationship between contingent negative variation (CNV) and arousal level which was influenced by extraneous environment. As an extraneous stimulant, stimulation by light was adopted, and five levels of luminance conditions, 10 cd/m2, 100 cd/m2, 320 cd/ m2, 1,000 cd/m2, and 1,800 cd/m2 were provided randomly. Under five luminance conditions, seven subjects who had been accustomed a measurement of CNV executed simple reaction time tasks to evoke CNV. Outside CNV, spontaneous EEG prior to S1 was measured as an indicator for arousal level. As a result, a negative correlation existed between the logarithm of luminance and the relative power value of alpha waves at Fz. Otherwise, an increase in luminance caused an increase in CNV amplitude until the luminance level reached 320 cd/m2, beyond which however CNV amplitude was found to decrease. These tendencies were most remarkable in the phase of early CNV at Fz. The low amplitude of early CNV seen in the high luminance conditions was inferred to have been induced by excessive arousal state because of the low relative power value of alpha waves, while the low amplitude in the low luminance conditions was inferred to have been induced by low arousal state because of the high relative power value of alpha waves. However, changes in arousal level by light stimulus caused no effect on reaction time. From these findings, it was suggested that a definite "inverted-U" relationship existed between the change in arousal level by light stimulation and resultant CNV, and that it could be discriminated as to whether reduction in CNV is caused by excessive arousal effect of environment by analyzing spontaneous EEG preceding S1.

Adult

Evaluation of mental strain by palm sweating during short-term memory task.

This paper reports on the investigation of palm sweating during short-term memory tasks and testing the availability of the amount of palm sweating for an index evaluating mental strain. Six male subjects performed sets of thirty tasks with digit strings ranging from 4 to 9 digits at random order. The correctness of recalled answer, subjective difficulty for mental stress and palm sweating at each task were recorded. The amount of palm sweating (PS) was measured using hygrometry with a ventilated capsule attached on the left palm. Correct answer rates suddenly decreased over 7 digits. Subjective difficulty tended to increase with an increase in string-length. PS tended to decrease exponentially with the repetition of tasks at each string-length, and the exponential regression curve was fitted between PS and order in tasks at each string-length. Estimated PSs were obtained at 1st, 15th, and 30th tasks from the regression curves. Estimated PS at 1st task tended to increase in proportion to string-length. Each estimated PS at both 15th and 30th tasks had a threshold for increasing. Also, estimated PS increased in proportion to the string-length at no less than the threshold. The thresholds were 5 digits at 15th and 6 digits at 30th task. These present findings suggest that PS is an index available for measuring mental strain. Also, this index describes the level quantitatively in adaptation for mental stress.

Adult

Effects of wearing compression stockings on cardiovascular responses.

To investigate the effects of wearing compression stockings on cardiovascular responses, the heart rate (HR), cardiac output (Q) measured by CO2 rebreathing method, and oxygen intake were measured at rest in a supine position for 40 min and standing position for 120 min. Six female subjects wore the compression stockings after 20 min of rest at supine position. The oxygen intake and ventilation showed no significant difference between with and without the stockings. Q at standing position was lower than that at supine position by an act of hydrostatic pressure. However this decrease was lower with stockings than that without stockings. The compression stockings used in this study might improve the venous return to the heart. However, the subjects complained of discomfort due to the high clothing pressure. In the second experiment, the authors estimated the minimum pressure required in improving the venous return. The subjects wore the trousers having two bladders inflated by air pressure. The trousers could compress the leg (contain the foot) and thigh individually. From the relationship between air pressure and Q, the estimated minimum pressures were 17 mmHg for the leg and 15 mmHg for the thigh.

Bandages

Improvements on a design of girdle by using cardiac output and pressure sensation.

To improve the design of the girdle which was a type of compression clothing, two kinds of experiments were carried out. At first, the degree of blood disturbance from wearing the girdles was evaluated by the cardiac output (Q). Q was significantly decreased with normal and small sized girdle was not significant. The practical clothing pressure was the positions with small sized girdle was not significant. The practical clothing pressure was the highest at the groin. Therefore, the relationship between the pressure applied to the groin by the cuff and Q was investigated. Q decreased linearly with an increase in pressure. The estimated minimum pressure required in maintaining the blood circulation was 14.1 mmH. To restrain the clothing pressure below that value, the form and material of the form and material of the bandage attached to the groin were designed and then 4 types of trial models were made. The designed bandage, as compared with that of ready-made, has a large form of stretchable material and its length in contact with the groin line was long. Q did not decrease by wearing one of them at supine position and at supine position after the sitting position. Furthermore, subjective discomfort also decreased.

Adult

Dark adaptation curve during body temperature decrease.

To investigate the effect of body temperature decrease which occurred along with cold exposure and menstrual cycle on visual acuity, the dark adaptation curve (DAC), heart rate (HR) and tympanic membrane temperature (Tty) were measured at thermoneutral (29 degrees C) and cold (15 degrees C) in both follicular and luteal phases in menstrual cycle. Tty at thermoneutral and cold exposure in follicular phase were significantly lower than those in luteal phase. The degree of decrease in Tty by cooling in follicular phase was not significantly larger than that in luteal phase. HR was decreased significantly by cooling in both phases, while the difference between the two phases was not significant. DAC during cold exposure was lower than that during thermoneutral condition in both phases. Furthermore, the curve obtained during cooling in follicular phase was lower than that during cooling in luteal phase. However, DAC obtained by a subject who showed an increase of Tty by cold exposure in both phases was higher than that at thermoneutral. Even in thermoneutral in luteal phase, DAC during head cooling was significantly lower than that during thermoneutral. These results suggest that the brightness sensitivity in scotopic vision might be increased by a decrease of body temperature and the light threshold during dark adaptation threshold may be related to the change of Tty.

Adult

Effects of body temperature decrease on color sensation.

To investigate the effects of body temperature decrease which occurred along with cold exposure and menstrual cycle, on color sensation, differential limen (DL) and points of subjectively equality (PSE) or red, green, blue and gray colors were measured by using methods of limit in six young female subjects. also, the subjectively preferred complexion was selected. The lowest value in tympanic membrane temperature (Tty) was observed under the cold exposure condition at 15 degrees C in follicular phase. DL of gray obtained during cooling was significantly lower than that during thermoneutral condition in follicular phase. However, DL of green, red and blue were not changed by cold exposure in both menstrual phases. The Munsell value of subjectively preferred complexion selected during cooling was significantly lower than that obtained during thermoneutral condition in follicular phase. Compared with the distribution of Munsell hue of chips selected as preferred complexion in thermoneutral condition, the hue selected in cooling was not shifted to a more reddish one. These results suggest the possibility that brightness sensation rather than color sensation might be increased due to Tty decrease.

Adult

Effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in patients with gastric cancer.

The effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in gastric cancer patients was investigated. A 2-mg dose of lentinan was administered to 12 patients intravenously twice, the first at 3-9 days before and the second the day before surgery. The results were then compared with a control group without lentinan administration comprising 12 patients. Regarding peripheral blood and lymph nodes without metastasis, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu7, and anti-Leu11 were analyzed by flow-cytometry. As for tumor tissues, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu11, and anti-M3 were analyzed after immunohistochemical staining. There were no significant changes in the lymphocyte subsets of peripheral blood between the two groups. In the lymph nodes, the CD4 cell ratios increased; otherwise in regard to tumor-infiltrating lymphocytes (TILs), the number of CD4, Leu11 and LeuM3 cells showed a prominent increase. Therefore, lentinan was observed to produce different effects in accordance with the subjective organs.

Aged

6-[18F]fluorodopa metabolism in patients with hemiparkinsonism studied by positron emission tomography.

A group of 10 healthy control subjects and 10 patients with hemiparkinsonism (HD) were studied by positron emission tomography (PET) using 6-[18F]fluorodopa (FDOPA). FDOPA metabolism in the caudate nucleus and the putamen was separately estimated by measuring target-to-background ratios (TBRs) using composite images added between 30 and 60 min after FDOPA injection and by TBR-versus-time slopes during PET study. TBRs in the caudate nucleus and the putamen were 1.81 +/- 0.23 (mean +/- SD) and 1.92 +/- 0.28 in the 10 controls, respectively. In HD patients, on the dominantly affected hemisphere related to main clinical symptoms, TBRs were significantly decreased in the caudate nucleus (P < 0.01) and the putamen (P < 0.05) compared with those in the corresponding areas on the contralateral hemisphere, though those TBRs on both hemispheres were significantly decreased compared with the TBRs of normal subjects (P < 0.01). TBRs and TBR slopes in both the caudate nucleus and the putamen were correlated with disease severity according to Hoehn and Yahr. On the dominantly affected hemisphere, TBR and TBR slopes in the putamen were well correlated with individual clinical measures for bradykinesia and rigidity, and those in the caudate nucleus were also correlated with the severity of tremor. Our data suggest that in HD patients, PET study using FDOPA may provide unique and efficient information on the dysfunction of the dominantly affected caudate nucleus and the putamen which are correlated with diseased severity and individual clinical symptoms.

Adult