Biomedical subjects

H Toyama

Publications and source records attributed to H Toyama.

At least 55 records · Page 3Linked to original sources

PubMed1999

Improved signal-to-noise ratio in parametric images by cluster analysis.

Parametric images are formed by analyzing the concentration history of every voxel in PET data sets. Because PET concentration data at the voxel level are rather noisy, noise propagation into the parametric image is often quite noticeable. To address this problem, a model-based clustering method has been developed to generate parametric images. The basic idea of the clustering method is to average over voxels whose concentration histories have the same shape. We applied the method to a two-parameter (K1, k2) compartment model of local cerebral blood flow. The statistic R = integral tC(t) dt/integral C(t) dt= integral te-k2t multiply sign in circle Ca(t) dt/integral e-k2t multiply sign in circle Ca(t) dt classifies curves in terms of k2, where C(t) and Ca(t) denote the tissue and blood concentration histories, respectively, and multiply sign in circle is the convolution operator. Simulation studies of noise propagation in the clustering statistic showed that 30% voxel noise yielded a 2% standard deviation in R. Parametric images of blood flow and partition coefficient were computed for an O15 study, with and without clustering. Cluster size affected bias, statistical precision, and computation time. With clusters of 400 voxels, the variance of the flow parameter was around 1/50 smaller with clustering, with negligible bias and a computation time of 30 s on a 64-MHz workstation for 15 x 128 x 128 images with MATLAB 5.1.

Adult↗

PubMed1999

Evaluation of asialoglycoprotein receptor imaging agent as a marker of hepatic ischemia-reperfusion injury and recovery.

Protection of hepatocytes from ischemia-reperfusion injury is a clinically important issue. The purpose of this study was to evaluate changes in acute liver damage and recovery after ischemia-reperfusion in rats with asialoglycoprotein receptor (ASGP-R) ligand. Ischemia was induced by clamping the hepatoduodenal ligament for 90 min. At 1, 3, 24, 48 hr, 1 and 2 wk after reperfusion, I-125-GSA was injected. Five min after injection, blood samples were obtained and the liver was removed. Several regions from each lobe were dissected, weighed and counted. Mean uptakes (% dose/g) in the liver and blood samples were calculated. Histologic sections stained with hematoxylin-eosin (H-E) stain showed ischemic damage at 1 and 3 hr, and focal hepatocyte necrosis at 24 hr. Predominant massive necrosis was not seen. The mitotic index with H-E stain and proliferating cell nuclear antigen (PCNA) labeling index were highest at 1 wk, indicating liver regeneration. At 1 and 3 hr, liver uptake was significantly decreased, and blood uptake was significantly increased, indicating decreased tissue blood flow and ischemic damage. Liver uptake showed significant increases at 48 hr and 1 wk, and was the highest at 1 wk, indicating liver regeneration during the convalescence stage. ASGP-R binding may provide valuable information on ischemia-reperfusion injury and recovery.

Animals↗

PubMed1999

Comparison of three PET dopamine D2-like receptor ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, in rats.

We studied the tracer kinetics of three dopamine D2-like receptor ligands, [11C]raclopride ([11C]RAC), [11C]nemonapride ([11C]NEM) and [11C]N-methylspiperone ([11C]MSP), in anesthetized rats by tissue dissection, ex vivo ARG and PET in order to clarify their characteristics for PET imaging. The in vivo affinity of the three ligands for the striatum ([11C]MSP > [11C]NEM > [11C]RAC) obeyed the in vitro affinity for dopamine D2 receptors. The affinity of [11C]RAC and [11C]MSP for the cerebellum was very low, but the affinity of [11C]NEM for the cerebellum was compatible to that for the cortex and was not to be ignored. Also the affinity of [11C]MSP for the cortex was relatively high. [11C]RAC showed the highest selectivity. The striatal PET image with [11C]RAC was clearer than that with [11C]NEM or [11C]MSP, but the activity decreased much faster than that measured by tissue dissection because of the partial volume effect. The striatal activity with [11C]NEM remained high and that with [11C]MSP gradually increased. [11C]RAC and [11C]MSP, but not [11C]NEM, showed a high accumulation in the periorbital region.

Animals↗

PubMed1999

Preserved benzodiazepine receptors in Alzheimer's disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF.

This study evaluates the regional cerebral blood flow (CBF) with H2(15)O-PET and the distribution of central benzodiazepine receptor (BZR) with C-11 flumazenil (FMZ) by PET and I-123 iomazenil (IMZ) by SPECT in Alzheimer's disease (AD). In AD, whereas the CBF was diminished in the frontal, temporal, parietal, and occipital cortex, the distribution volume of FMZ and delayed activity of IMZ were relatively preserved in these cortices, suggesting that the BZR reduction, reflecting neuronal loss, is less prominent than the CBF suppression. The mini-mental state examination score (MMS) was weakly correlated with the CBF in the parietal cortex but not with BZR. It is speculated that the neuronal density reflected by BZR is less impaired than the neuronal function assessed with blood flow in the association cortex of AD. High correlation was found between the uptake of FMZ and the delayed activity of IMZ. The delayed image of IMZ-SPECT is clinically useful to evaluate the preservation of neuronal density in the affected temoporoparietal association cortex in AD.

Aged↗

PubMed1999

Phase changes caused by hyperventilation stress in spastic angina pectoris analyzed by first-pass radionuclide ventriculography.

To understand the effect of hyperventilation (HV) stress in patients with spastic angina, left ventricular (LV) contraction was analyzed by quantitative phase analysis. The study was performed on 36 patients with spastic angina pectoris, including vasospastic angina pectoris (VspAP: 16 patients) and variant angina pectoris (VAP: 20 patients). First-pass radionuclide ventriculography (first-pass RNV) was performed at rest and after HV stress, and standard deviation of the LV phase distribution (SD) was analyzed. The SD was lower in patients with VspAP than in VAP (12.8+/-1.4 degrees vs. 14.6+/-2.2 degrees, p < 0.005) at rest. After HV stress, the SD (HVSD) tended to increase in VspAP patients (62.5%), whereas the SD decreased in VAP patients (70%). Due to HV stress, the percentage change in SD (%SD) in VspAP patients was 8.9+/-23.7% whereas that in VAP patients was -9.1+/-17.3% (p < 0.01). Moreover, phase histograms were divided into HVSD increase and HVSD decrease groups. The HVSD increase group had a decrease of HVEF, but the HVSD decrease group tended to have more decreased HVEF than the HVSD increase group. These results indicate that spastic angina pectoris patients show various responses to HV stress. The HVSD increase group might have additional myocardial ischemia due to regional coronary spasm. In contrast, in the HVSD decrease group severe LV dysfunction or diffuse wall motion abnormality might have been generated, and this caused a reduction in the SD value. Phase analysis would therefore add new information regarding electrocardiographically silent myocardial ischemia due to coronary spasm, and HV stress might increase sensitivity for the detection of abnormalities in quantitative phase analysis, especially in VspAP patients.

Adult↗

PubMed1999

Arthrodesis of the hip joint using an external fixator.

Arthrodesis of the hip has been plagued by high rates of nonunion, and by complications associated with prolonged cast immobilization. To prevent these problems, we devised a procedure for hip arthrodesis using an external fixator in combination with internal fixation at the fusion site. We have treated nine patients with this technique. All of the arthrodeses were solidly united without wound infections at the most recent follow-up. Patients were able to leave their hospital bed and walk on the affected limb with a cane shortly after surgery. This was possible because the external fixator was low in profile, as it was applied from the anterosuperior iliac spine to the femoral shaft, and provided rigid stabilization of the arthrodesis. The technique resulted in a reduction in the period of bed rest, immediate postoperative mobilization, shorter periods of hospitalization, no limitation in the range of knee and ankle motion, improvement in the patient's ability to carry out the personal hygiene, and fewer complications.

Activities of Daily Living↗

PubMed1999

Crystallization and preliminary diffraction studies of two quinoprotein alcohol dehydrogenases (ADHs): a soluble monomeric ADH from Pseudomonas putida HK5 (ADH-IIB) and a heterotrimeric membrane-bound ADH from Gluconobacter suboxydans (ADH-GS).

Crystals of a soluble monomeric quinocytochrome alcohol dehydrogenase (ADH-IIB) and of a trimeric membrane-associated quinocytochrome alcohol dehydrogenase (ADH-GS) have been obtained. The ADH-IIB crystals are triclinic, with one monomer in the unit cell, and were obtained in the presence of PEG 8000, sodium citrate, HEPES buffer and 2-propanol. X-ray data were collected at 110 K to 1. 9 A resolution (R(merge) = 6.4%) and the orientation of a methanol dehydrogenase search molecule (from Methylophilus methylotrophus W3A1) was obtained by molecular replacement. Preliminary refinement of this model (10.0-3.0 A resolution, R = 0.37, R(free) = 0.40) led to tentative identification of the two highest peaks in a native anomalous difference Fourier map as the Fe atom of the heme and a calcium ion interacting with the PQQ prosthetic group. The ADH-GS crystals are tetragonal, displaying six similar lattices, both primitive and centered, and were grown by the sitting-drop method after replacement of Triton X-100 by dodecylmaltoside or octaethylene glycol monododecyl ether in the presence of ammonium sulfate and sodium acetate buffer, with and without PEG 3500 and calcium ion. The best diffraction is obtained at 110 K where the resolution extends to about 4 A in the a and b directions and about 3 A in the c direction.

Alcohol Oxidoreductases↗

PubMed1999

Purification and characterization of methylamine oxidase induced in Aspergillus niger AKU 3302.

Crude extract of Aspergillus niger AKU 3302 mycelia incubated with methylamine showed a single amine oxidase activity band in a developed polyacrylamide gel that weakly cross-reacted with the antibody against a copper/topa quinone-containing amine oxidase (AO-II) from the same strain induced by n-butylamine. Since the organism cannot grow on methylamine and the already known quinoprotein amine oxidases of the organism cannot catalyze oxidation of methylamine, the organism was forced to produce another enzyme that could oxidize methylamine when the mycelia were incubated with methylamine. The enzyme was separated and purified from the already known two quinoprotein amine oxidases formed in the same mycelia. The purified enzyme showed a sharp symmetric sedimentation peak in analytical ultracentrifugation showing S20,w0 of 6.5s. The molecular mass of 133 kDa estimated by gel chromatography and 66.6 kDa found by SDS-PAGE confirmed the dimeric structure of the enzyme. The purified enzyme was pink in color with an absorption maximum at 494 nm. The enzyme readily oxidized methylamine, n-hexylamine, and n-butylamine, but not benzylamine, histamine, or tyramine, favorite substrates for the already known two quinoprotein amine oxidases. Inactivation by carbonyl reagents and copper chelators suggested the presence of a copper/topa quinone cofactor. Spectrophotometric titration by p-nitrophenylhydrazine showed one reactive carbonyl group per subunit and redox-cyclic quinone staining confirmed the presence of a quinone cofactor. pH-dependent shift of the absorption spectrum of the enzyme-p-nitrophenylhydrazone (469 nm at neutral to 577 nm at alkaline pH) supported the identity of the cofactor with topaquinone. Nothern blot analysis indicated that the methylamine oxidase encoding gene is largely different from the already known amine oxidase in the organism.

Amino Acid Sequence↗

PubMed1999

Perceptibility of body position in anteroposterior direction while standing with eyes closed.

The perception of body position in the anteroposterior direction was investigated by evaluating the reproducibility of the position from a quiet standing posture to forward or backward leaning posture with eyes closed. The subjects were 10 healthy male undergraduates, aged 20 to 28 years. The standing position was represented by the pressure center of the foot, which was shown by the relative distance (%) from the heel to the length of the foot. The reference positions of the pressure center of the foot were set at 10% increments from 20 to 80% of the length of the foot. The subjects attempted to reproduce each reference position 10 times, and the absolute and constant errors of the reproduced position were analyzed. The absolute errors at reference positions of 30 to 60% were distinctly larger than those at the other reference positions. This indicated that the perception of standing positions from 30 to 60% was less accurate. The constant errors at the reference positions of 40 to 60% were significantly positive, which meant that the reproduced position was located farther forward than the reference position.

Adult↗

PubMed1999

Starting position of movement and perception of angle of trunk flexion while standing with eyes closed.

The present study attempted to investigate the effect of position on the perception of angle of trunk flexion while standing. For this purpose, the range effect was factored out by setting the constant target angle at 10 degrees, with varied starting positions of trunk flexion. We found that subjects underestimated angle of trunk flexion when the starting position was close to a quiet standing posture, overestimated when close to maximum trunk flexion, and correctly perceived it when at the middle position. Less perceptual distortion was observed at the positions close to maximum trunk flexion in the present study than in our previous one, in which various target angles of trunk flexion were reproduced from a quiet standing posture. The reduced distortion in the present study was believed to have resulted from factoring out the range effect. The flexion angle of the hip joint changed in tandem with that of the trunk, while very little movement was observed in the ankle, knee, and neck joints. Judging from the changing pattern of hip-joint angle, the muscle activity of the erector spinae and biceps femoris increased gradually to 90 degrees trunk flexion. In contrast, the actual increment of muscle activity reached zero or a minimum value at the middle angles as the angle of trunk flexion increased. It was assumed that the abrupt change in kinesthetic information associated with muscle activity exerted a great influence on the perception of trunk flexion.

Hip Joint↗

PubMed1999

Construction of cellulase hyperproducing strains derived from polyploids of Trichoderma reesei.

The mycelial mat of Trichoderma reesei strain QM 6a was treated with 0.1% (w/v) colchicine solution for 14 days and designated M14. The cellulase productivity of strain M14 was not much higher than that of the original strain. When conidia of M14 were treated with ethylmethane sulphonate (EMS) solution, the cellulase hyperproducers, M14-1 and M14-2, were isolated using a selection medium containing Avicel. The DNA content of M14-1 and M14-2 was higher than that of the original strain. Cellulase productivity per mycelium of these strains increased and was higher than that of the original strain. The cellulase productivity did not change through ten generations when these strains were cultivated successively on a medium containing Avicel. It was concluded that cellulase hyperproducers, whose cellulase productivity per mycelium increased, could be obtained when the conidia of strain M14 were treated with EMS.

Cellulase↗

PubMed1998

Construction of insertion and deletion mxa mutants of Methylobacterium extorquens AM1 by electroporation.

Methylobacterium extorquens AM1 is a pink-pigmented facultative methylotroph which is widely used for analyzing pathways of C1 metabolism with biochemical and molecular biological techniques. To facilitate this approach, we have applied a new method to construct insertion or disruption mutants with drug resistance genes by electroporation. By using this method, mutants were obtained in four genes present in the mxa methylotrophy gene cluster for which the functions were unknown, mxaR, mxaS, mxaC and mxaD. These mutants were unable to grow on methanol except the mutant of mxaD, which showed reduced growth on methanol.

Alleles↗

PubMed1998

Data base and management system for clinical positron emission tomography (PET) studies.

A data base and management system connected to an image analysis system has been developed and utilized for clinical positron emission tomography (PET). This data base system, 1) is based on "GBASE", a general purpose data base, which runs on a UNIX work station, 2) works on a network file system and is connected to PET cameras and other data acquisition devices as well as to an image analysis system "Dr.View", 3) centrally manages the data stored in a data storage unit, 4) is easily modifiable and expandable, and 5) has a human friendly interface which requires minimum operation for registration, retrieval and management. We have been using this system to handle clinical PET data for seven years and have optimized the data base schema. As a result, this system has become a truly practical tool for the daily operation and is well-received by technologists, nuclear physicians and attending physicians.

Brain↗

PubMed1998

Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model.

I-123-iomazenil is a SPECT probe for central benzodiazepine receptors (BZR) which may reflect intact cortical neuron density after ischemic insults. We evaluated whether neuronal damage in rats could be characterized by iomazenil as compared with cerebral blood flow (CBF). Serial changes in I-125-iomazenil for BZR and I-123-IMP for CBF were analyzed after the unilateral middle cerebral artery occlusion in rats by using an in vivo dualtracer technique. Uptake ratios of affected to contralateral regions were calculated. The iomazenil as well as IMP were decreased in all regions except for the cerebellum (remote area). Both iomazenil and IMP increased over time except in the temporal region (ischemic core). The iomazenil uptake was higher than IMP except in the ischemic core between 1 and 3-4 wk when iomazenil was lower than IMP. Iomazenil showed a moderate decrease in the proximal and middle parietal regions (peri-infarct areas) at 3-4 wk. The triphenyl-tetrazolium-chloride (TTC) stain at 1 wk demonstrated unstained tissue in the temporal region indicating tissue necrosis. With hematoxylin-eosin (HE) stain at 1 wk, widespread neuronal necrosis with occasional intact neurons were found in the proximal parietal region, and isolated necrotic neurons were represented in the distal parietal region. Iomazenil correlated well with the neuron distribution and the finding of a discrepancy between iomazenil and IMP might be useful in evaluating the neuronal damage.

Animals↗

PubMed1998

Metabolite analysis of [11C]flumazenil in human plasma: assessment as the standardized value for quantitative PET studies.

Analysis of carbon-11 labeled metabolites in plasma was carried out during positron emission tomography (PET) studies with a central benzodiazepine receptor ligand [11C]flumazenil ([11C]FMZ) in 24 human subjects (14-76 y.o.) including five normal volunteers and 19 patients with neurological disorders. Arterial plasma samples were obtained at 3, 5, 10, 15, 20, 30 and 60 min after i.v. injection of the tracer, and were analyzed by high-performance liquid chromatography. The rate of plasma [11C]FMZ degradation was associated with a large individual variation, but no significant difference was found in the degradation of [11C]FMZ either between male and female, young and old, or between normal subjects and patient groups. When the mean fraction of unchanged [11C]FMZ at each time point was used instead of individually measured metabolite data for the arterial input function, as much as a 30% error occurred in the distribution volume of the [11C]FMZ binding in the brain. These results indicate that the mean percentage of unchanged [11C]FMZ fraction in subjects cannot be used as the standardized value, and that the analysis of metabolites in plasma is necessary to determine the exact arterial input function for quantitative PET measurement.

Adolescent↗

PubMed1998

Positron emission tomography reveals changes in global and regional cerebral blood flow during noxious stimulation of normal and inflamed elbow joints in anesthetized cats.

In cats the global (gCBF) as well as the regional cerebral blood flow (rCBF) and blood pressure were measured before, during, and after noxious inward and outward rotations of normal and inflamed elbow joints. The animals were anesthetized with halothane and immobilized by gallamine triethiodide. The gCBF as well as the rCBF were measured using positron emission tomography (PET) with a camera specifically designed for use in small animals. Slow intravenous bolus injections of 15O-labeled water were followed by 3-min acquisition of regional radioactivity starting at the time of injection. In all experiments the gCBF as well as the blood pressure were increased by noxious inward-outward rotations of the normal and of the inflamed joint, whereas the blood pressure and the rCBF remained unchanged during bolus injections under control conditions (without any joint movement). Movements of the inflamed joint evoked significantly greater increases in blood pressure and gCBF than corresponding ones of the normal joint. These increases in gCBF were paralleled by increases in rCBF along the complete anterior to posterior axis of the brain. Again, the increases in rCBF were larger, more extensive and more uniform following the stimulation of the inflamed joint relative to the results obtained with stimulation of the normal joint. No significant laterality was seen, but when an atlas-based region of interest (ROI) analysis was carried out and when the individual variations in rCBF were removed with two-way ANOVA, significant differences were disclosed in rCBF between the stimulated condition and the resting condition in a large number of brain regions. In particular, noxious rotation of the normal (right) elbow joint induced a significant increase in rCBF over the cerebral cortex and in the right thalamus and hippocampus. The same stimulation of the (left) inflamed joint induced a significant increase in rCBF throughout the brain; the biggest increase being over the right posterior cortex. It is concluded that under the conditions of the present experiments the generally accepted autoregulation of the cerebral blood flow is not fully functioning, and various factors that may be responsible for this failure (which obscures rCBF differences) are discussed. The more pronounced increases in rCBF when moving inflamed joints instead of normal ones is thought to be a direct consequence of the peripheral sensitization of the articular nociceptors and the consequent central hyperexcitability induced in the articular nociceptive pathways.

Anesthesia↗

PubMed1998

Posthyperventilatory steal response in chronic cerebral hemodynamic stress: a positron emission tomography study.

BACKGROUND AND PURPOSE: The alteration of regional cerebral blood flow (CBF) during and after hyperventilation was measured using positron emission tomography (PET) to determine the circulatory response induced by daily respiratory changes in the cerebral area under chronic hemodynamic stress. METHODS: Three normal volunteers and 12 patients with an obstruction of major cerebral arteries underwent PET measurements of the CBF after an injection of H2(15)O: (1) in the resting condition, (2) during hyperventilation (HV scan), (3) 1 to 3 minutes after hyperventilation (post-HV scan), (4) during the inhalation of 5% CO2, and (5) after an injection of acetazolamide. Eleven patients also underwent a 15O gas study to measure CBF, oxygen extraction fraction (OEF), and cerebral blood volume (CBV). RESULTS: (1) In 9 patients, the CBF value in the post-HV scan was lower than that in the HV scan in 1 or more regions in the area of the obstructed arteries, although the PaCO2 level during the post-HV scan was higher than that during the HV scan in all patients. All control regions in the patients and in the normal volunteers showed an elevated CBF in the post-HV scan compared with the HV scan. (2) The negative post-HV response (posthyperventilatory steal) was prominent in 4 patients with moyamoya vessels and in another 5 patients with atherosclerotic disease who had PET evidence of hemodynamic stress (elevated CBV or OEF). (3) The regional pre- to post-HV change in CBF was significantly correlated with the CBF responses to acetazolamide and CO2. CONCLUSIONS: Vasodilatation after the termination of hyperventilation in the normal areas induces a steal response in the cerebral area suffering from hemodynamic stress and may cause profound hypoperfusion in everyday situations. This phenomenon may be important to our understanding of the clinical symptoms and the natural course of chronic cerebral occlusive disease bearing hemodynamic stress.

Acetazolamide↗

PubMed1998

Magnetic resonance cisternography for visualization of intracisternal fine structures.

OBJECT: To assess its usefulness in demonstrating cisternal anatomy, the authors investigated magnetic resonance (MR) cisternography in which a heavily T2-weighted turbo spin-echo method was used to visualize normal anatomical fine structures and lesions in the basal cisterns in 20 healthy volunteers and 43 patients. The authors applied peripheral pulse gating, which had been optimized to reduce artifacts in the cisterns attributable to cerebrospinal fluid (CSF) flow. METHODS: The detectability of each cranial nerve was determined in healthy volunteers. The first, second, and third nerves and the seventh-eighth nerve complex were clearly visualized in all participants; the fifth nerve was clearly seen in 80% and the sixth cranial nerve in 50%. The fourth nerve and the ninth through 12th nerves were difficult to identify individually, except in some volunteers. To reduce artifacts caused by fast CSF flow, we determined the delays as a function of the time elapsed between two consecutive peaks of pulse wave in a peripheral pulse gate (P-P interval) at which there was reversal of flow direction to minimize the CSF flow-related artifact. Using peripheral pulse gating and a time delay of 30% of the R-R interval, the authors succeeded in minimizing the CSF flow-related artifacts. Magnetic resonance cisternography appears to be very useful for demonstrating intracisternal fine anatomy and enhancing the contours of the juxtacisternal lesion. A minute amount of CSF interposed between lesions and normal structures such as nerves, vessels, or bone structures can be detected by means of this sequence. In patients with facial spasm, axial images and oblique coronal images obtained in a plane parallel to the seventh-eighth cranial nerve complex demonstrated vascular compression in all 13 patients. The MR cisternography finding of compression was confirmed in all nine patients who underwent microvascular decompression. CONCLUSIONS: Magnetic resonance cisternography appears to show great promise for evaluation of patients with neurovascular compression or tumors in and around the basal cisterns; the procedure adds only a small amount of imaging time.

Adult↗