Biomedical subjects

H Toyama

Publications and source records attributed to H Toyama.

At least 73 records · Page 4Linked to original sources

PubMed1998

Evaluation of carbon-11-labeled KF17837: a potential CNS adenosine A2a receptor ligand.

UNLABELLED: The 11C-labeled KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxa nthine) was evaluated as a PET ligand for mapping adenosine A2a receptors in the central nervous system (CNS). METHODS: The regional brain distribution of [11C]KF17837 and the effect of adenosine antagonists on the distribution were measured in mice by the tissue sampling method. In rats, the regional brain uptake of [11C]KF17837 and the effect of carrier KF17837 was visualized by autoradiography. Imaging of the monkey brain with [11C]KF17837 was performed by PET. RESULTS: In mice, a high uptake of [11C]KF17837 was found in the striatum in which A2a receptors were highly enriched. The uptake was decreased by co-injection of carrier KF17837 or a xanthine-type A2a antagonist CSC but not by nonxanthine-type A2a antagonists ZM 241385 or SCH 58261, or an A1 antagonist KF15372. In the rat brain, [11C]KF17837 was accumulated higher in the striatum than in other brain regions, and the uptake was blocked by co-injection of carrier KF17837. In a monkey PET study, a high striatal uptake of radioactivity was observed. CONCLUSION: Carbon-11-KF17837 binds to adenosine A2a receptors in the striatum. However, the presence of an unknown but specific binding site for xanthine-type compounds also was suggested in the other brain regions. The results also suggested that the in vivo receptor-binding sites of xanthine-type ligands are slightly different from those of nonxanthine-type A2a antagonists.

Animals↗

PubMed1998

[Creation of a dynamic digital phantom and its application to a kinetic analysis].

A dynamic digital brain phantom was created from the MRI to evaluate visually the relationship between the noise and the error in the parameter estimates in the PET kinetic analysis. This phantom incorporates the noise level depending on administration dose, camera efficiency and the data acquisition schedule. We simulated a serial dynamic scan with 18F-FDG or 11C-flumazenil, assuming 2-tissue 3-parameter model and 1-tissue 2-parameter model, respectively, and the sampling schedule was determined according to the clinical examination. The noise in the tissue time activity curve in FDG had a peak in the first minute and decreased thereafter, whereas the noise increased gradually in the flumazenil study after the initial peak due to radioactivity decay. We examined the relationship between the noise level and the error in the parameter estimates. Both mean absolute differences between true and estimated values and standard deviation became large, and the quality of the parametric images became poor with increasing noise level. This simulation was compared with human tissue time activity curves and parametric images, which were obtained with 100 MBq administration dose in FDG study and 430 MBq in flumazenil study. We inferred that the noise level in the human study was 10-20% in FDG, and 20-40% in flumazenil, and the error in the estimated parameter of K-complex in FDG study was about 20%, that of DV in flumazenil study was 2%.

Brain↗

PubMed1998

Bentall operation, total aortic replacement and mitral valve replacement for a young adult with Marfan syndrome: a case of three-staged operation.

In Marfan syndrome, the most common cardiovascular abnormalities are dilatation of the aorta and aortic valve regurgitation in adult patients. Mitral valve dysfunction is the most common cause of morbidity and mortality in infants and children with Marfan syndrome, and is not frequently operated on in adult Marfan patients who undergo surgery for diseases of the aortic root and total aorta. This report describes a successfully three-staged operation for a 24 year-old man with Marfan syndrome who underwent an emergent Bentall operation and aortic arch replacement, total aortic replacement and mitral valve replacement over 2 years. Mitral valve regurgitation was mild but increased after the second operation. The graft was tightly adhesive and invasive to the sternum. Endoscopic view was helpful to avoid graft damage at resternotomy. The postoperative course was uneventful in each operation. Microscopic examination of the mitral valve leaflets showed abnormal increase of mucopolysaccharides, and disruption and fragmentation of elastic fibers.

Adult↗

PubMed1998

[A modified method of cardiac functional analysis for ECG gated SPECT: study of functional G-maps].

To evaluate the cardiac function accurately using ECG gated SPECT images, we performed a modified method of cardiac functional analysis (Functional G-maps). One hour after the intravenous injection of 1,110 MBq of 99mTc-tetrofosmin, gated SPECT data was acquired dividing a cardiac cycle into 12 frames. Every short-axis images were usually reconstructed using first 11 of 12 frames. The reconstruction of these images was repeated performing slice thickness correction. Because the apex-to-base length is different at any frame during a cardiac cycle, 10 slices of short-axis images were obtained with the same thickness for each frame. Subsequently each short-axis image was divided by 40 radii, and the time activity curve was generated from the total counts included in each segment plus both neighboring segments. Afterwards the curve fitting was performed using the second reverse Fourier function. From fitted curves and their differentials, we estimated a variety of parameters including Max (End-systolic count), Min (End-diastolic count), %CI (Percent count increase), Uptake, PCR (Peak contraction rate), PDR (Peak distention rate) and CT (Contraction time). In 5 normal subjects, %Max was greater in the anterior and septal regions, whereas %Min was greater in the apex and lateral regions. %CI and %PCR were similarly greater in the septal, anterior and inferior regions. On the other hand, %PDR in the lateral or inferior region was lower than the values in the other regions. In conclusion, this modified method is expected to be useful for accurate assessment of regional cardiac function and myocardial perfusion.

Adult↗

PubMed1997

Effects of reserpine treatment on the dopamine receptor binding of [3H/11C]nemonapride in the mouse and rat brain.

We investigated the effect of reserpine treatment on the striatal uptake of a radiolabeled dopamine D2-like receptor ligand nemonapride (NEM). In mice, the uptake of the [3H]NEM in the striatum, cortex and cerebellum was enhanced by the reserpine pretreatment. Neither the ratio of striatum to cerebellum nor that to cortex was affected by the reserpine pretreatment. In rats, ex vivo autoradiography showed no effect of the reserpine treatment on the striatal uptake of [11C]NEM or the striatum to cortex ratio. The results suggest that the receptor binding of NEM was not significantly influenced by reserpine-induced depletion of endogenous dopamine probably because of its high affinity for the receptors.

Animals↗

PubMed1997

Myocardial adenosine A2a receptor imaging of rabbit by PET with [11C]KF17837.

Adenosine A2a receptors are found in the endothelia, vascular smooth muscle cells and cardiac myocytes. The properties of a carbon-11 labeled A2a antagonist [11C]KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methy lxa nthine) for myocardial imaging were evaluated by dynamic PET scanning of the myocardium in rabbits. Myocardial uptake of [11C]KF17837 was clearly visualized by PET. The tracer was taken up at a high level by the myocardium immediately after the injection, and the myocardial level of radioactivity gradually decreased. On the other hand, an inactive [11C]Z-isomer of [11C]KF17837 showed a very low myocardial uptake and the myocardium was not visualized with a selective A1 antagonist [11C]KF15372. By co-injection with carrier KF17837 or a xanthine type A2a antagonist 7-chlorostyrylcaffeine (CSC), the myocardial uptake of [11C]KF17837 was completely blocked. The effect of non-xanthine A2a antagonists ZM 241,385 and SCH 58,261, which have a higher affinity than CSC, was smaller than that of the CSC. The effect of weak antagonists caffeine and alloxazine or a xanthine type A1 antagonist KF15372 on the radioactivity level was small. It is concluded that PET with [11C]KF17837 can image myocardial adenosine A2a receptors.

Animals↗

PubMed1997

A stereotaxic method of anatomical localization by means of H(2)15O positron emission tomography applicable to the brain activation study in cats: registration of images of cerebral blood flow to brain atlas.

In the neuronal activation study of normal animals, precise anatomical correlation, preferentially to a detailed brain atlas, is required for the activation foci co-registration. To obtain precise regional correlation between H(2)15O-PET images and the brain atlas, a method of stereotaxic image reorientation was applied to an activation study with vibrotactile stimulation. Cats anesthetized with halothane underwent repeated measurements of regional cerebral blood flow (rCBF) in the resting condition and during vibration of the right forepaw. The image set was adjusted three-dimensionally to the atlas. The postmortem brain was sectioned according to the atlas planes. The activated areas were determined by the stimulus-minus-resting subtraction images, and the areas were projected to the atlas. The PET images of the cat brain were compatible both to the postmortem brain slices and to the brain atlas. The activation foci obtained from the subtraction images corresponded to the area around the coronal sulcus, which is electrophysiologically known as the primary sensory area as described in the atlas. There were precise regional correlations between the PET image and anatomy in a PET activation study of the cat by means of stereotaxic image reorientation.

Animals↗

PubMed1997

Mechanical efficiency in hypertrophic cardiomyopathy assessed by positron emission tomography with carbon 11 acetate.

This study was performed to assess the relation between the regional work and oxidative metabolism in hypertrophic cardiomyopathy (HCM). By using carbon 11 acetate as a tracer of myocardial blood flow (%A(0)) and oxygen consumption (k value), 12 patients with HCM with asymmetric septal hypertrophy and 10 normal subjects were studied. Regional work rate (RWR) of the left ventricle was estimated by wall stress and wall thickness. %A(0) in hypertrophied septum was similar to that in nonhypertrophied free wall (92.6% +/- 2.8% vs 93.5% +/- 3.8%; p = not significant). However, oxygen consumption was significantly lower in hypertrophied septum than in nonhypertrophied free wall (0.043 +/- 0.011 vs 0.057 +/- 0.013 min(-1); p < 0.001). The k value in nonhypertrophied free wall was similar to the value observed in normal subjects (0.062 +/- 0.013). Average values for RWR in hypertrophied septum, nonhypertrophied free wall, and normal subjects were 0.26 +/- 0.07,0.62 +/- 0.02,and 1.98 +/- 0.15 J/cm3/ min, respectively. Furthermore, the analysis of covariance, in which the effect of RWR was removed as a covariate, revealed that the overall RWR-corrected k value was much larger in patients with HCM (0.109 vs 0.062, p < 0.0001) than expected from the decreased regional myocardial work, suggesting that there was a diffused inefficiency in oxygen consumption. We concluded, therefore, that the relative value of oxidative metabolism in patients with HCM is significantly higher than that of the normal subjects, suggesting the presence of reduced mechanical efficiency.

Acetates↗

PubMed1997

Normal perfusion pressure breakthrough syndrome in giant arteriovenous malformations.

The treatment of large, high-flow cerebral arteriovenous malformations is one of the most difficult operations which neurosurgeons encounter because of the complex surgery and the post-operative effects on the brain. We have evaluated 10 patients with large, high-flow AVMs who underwent surgical resection. Patients were investigated with contrast-enhanced computed tomography and magnetic resonance imaging, 1231-IMP single photon emission computed tomography (SPECT) studies of cerebral flow and cerebral vasodilatory function, intraoperative Laser Doppler flowmetry (4 or 10 patients), and conventional angiography. The volume of the arteriovenous malformation nidi ranged from 32.8 to 210.5 cc. SPECT imaging performed on the first post-operative day showed marked hyperperfusion in the brain tissue surrounding the resected nidus, and these regions were normal on images on the 7th post-operative day. Laser Doppler flowmetry showed sudden, and marked increase in CBF immediately following placement of temporary clips on the main feeding artery. Angiograms done on 7-14 days following surgery showed a stagnating artery, fragile vessel, and a prolonged circulation time. Our results indicate that pre- and post-operative SPECT study, especially a dynamic SPECT study done on the first post-operative day, was the most useful examination for ascertaining the post-operative normal perfusion pressure breakthrough.

Adolescent↗

PubMed1997

Mapping visual field with positron emission tomography by mathematical modeling of the retinotopic organization in the calcarine cortex.

We developed an objective and quantitative method of mapping the human visual field with positron emission tomography (PET) and magnetic resonance image (MRI). The regional cerebral blood flow (rCBF) images were acquired with H2(15)O-PET under visual fixation as well as under visual stimulation with flickering diodes arranged along the ring at 0 degree, 3 degrees, 7 degrees, 14 degrees, 21 degrees, or 29 degrees from the fixation point. After coregistration of PET and MR images, we extracted the surface of the calcarine cortex from the MR images and unfolded it to a two-dimensional (2-D) elliptic plane, on which the activated PET images were superimposed. Then we transformed the unfolded calcarine cortex into the visual field coordinates using the complex logarithmic function proposed by Schwartz. A large individual variation was observed in the retinotopical organization as well as in the morphology of the calcarine cortex. The formula was valid only within 15 degrees from the center of the visual field. The constant parameter in the formula was estimated to be 1.5. The cortical linear magnification factor was 12.1, 2.8, and 1.6 at 0, 5, and 10 degrees, respectively. The areas of the central 10 degrees and 40 degrees in the visual field correspond to 50% and 81% of the calcarine surface, respectively.

Adult↗

PubMed1997

Myocardial blood flow and metabolism in patients with hypertrophic cardiomyopathy--a study with carbon-11 acetate and positron emission tomography.

The underlying pathophysiology of hypertrophic cardiomyopathy (HCM) is still unclear. positron emission tomography is a suitable and promising technique for the detection of possible metabolic consequences of the disease. To assess regional myocardial blood flow and metabolism, 19 asymptomatic or only mildly symptomatic patients with HCM and 10 normal control subjects were studied using carbon-11 acetate and fluorine-18-labelled deoxyglucose (FDG) as tracers of myocardial blood flow (Ao), oxygen consumption (k), and exogenous glucose utilization. In the patients, regional Ao in the hypertrophied septum and apex (H) was similar to that in the nonhypertrophied free wall (N) (91.3 +/- 3.9% vs 92.9 +/- 3.1%; p = NS). However, the k values were significantly lower in H than in N (0.044 +/- 0.012 vs 0.060 +/- 0.016/min, p < 0.0001). The k value in N and normal control subjects (0.062 +/- 0.013) was similar. Postprandial FDG uptake was lower in H than in N (70 +/- 16 vs 91 +/- 7%; p < 0.0001) in 16 patients and slightly higher in 3 patients. Fasting FDG study showed increased FDG uptake in H in 3 out of 13 patients, suggesting a disorder of the myocardial microvascular circulation. A relative decrease in hypertrophied septal and apical oxidative metabolism and glucose utilization without any corresponding perfusion defect could reflect abnormal regional aerobic metabolism in the disproportionately thickened myocardium in patients with HCM. This suggests that a primary myocardial metabolic defect might be present in patients with HCM.

Adolescent↗

PubMed1997

[Comparison of the number of parameters using nonlinear iteration methods for compartment model analysis with 18F-FDG brain PET].

In the analysis of the brain kinetic images with 18F-FDG, compartment models with 3 or 4 parameters and an estimation method of nonlinear least squares (NLS) have been applied. We compared the Simplex method and the modified Marquardt method as an iterative NLS algorithm on the simulation data with variable noise. The estimated k-values were equal in the both algorithms. The calculation with modified Marquardt method was three times faster than that of the Simplex method. The dependence of modified Marquardt estimates on the initial values was larger than that of the Simplex, but the permissible initial value range was wide enough for clinical data. Therefore, the modified Marquardt method was found to be more suitable for the compartment model analysis of 18F-FDG than the Simplex method. We also compared the 3-parameter with 4-parameter models for 45 min and 120 min data acquired after administration. The 3-parameter model was suitable for the 45-minute data acquisition, and the 4-parameter model was suitable for the 120-minute data acquisition.

Algorithms↗

PubMed1997

Three-dimensional imaging of cortical structure, function and glioma for tumor resection.

UNLABELLED: A three-dimensional brain imaging protocol with PET and MRI was used to visualize the cortical structure in relation to brain function and glioma infiltration to determine tumor resectability. METHODS: Sixteen patients with glioma had a PET scan with 11C-methionine to visualize tumor infiltration. The PET images were co-registered to the patients' own MRI reconstructed to the three-dimensional brain surface images to indicate the gyral structure and the extent of tumor infiltration. Thirteen patients, who bore tumors adjacent to the language or motor cortex, had H2 15O activation study to locate the eloquent cortex. The area of tumor infiltration was superimposed on the brain surface images together with the language and/or motor cortex. RESULTS: When a tumor was located within a single gyrus without influencing surface cortical gyrus pattern, the motor and language areas were identified morphologically by three-dimensional surface image alone. However, when the tumor caused swelling and deformation of cortical structure, functional mapping with H2(15)O activation technique was essential in locating them correctly. In such cases, the combined mapping of the facial motor area with oral movement and the language area with word repetition was the most useful method to identify the parasylvian structure in the dominant hemisphere. Total or near total resection of low-grade glioma in eight patients and the effective decompression of the active part of the malignant glioma in four patients was completed without causing functional neurological deterioration. CONCLUSION: The three-dimensional expression of cortical structure and function combined with PET glioma imaging with 11C-methionine is useful for radical resection of cerebral glioma.

Adult↗

PubMed1997

Rapid diagnostic imaging of cancer using radiolabeled liposomes.

A novel tumor diagnostic imaging method was developed that allows tumor localization soon after administration of radiolabeled liposomes. Although previous studies showed that radiolabeled liposomes can reach various tumors in a short time, their blood clearance is slow, and the high blood background hinders early imaging. Therefore, we attempted to remove actively the liposomes from the circulation using the strong affinity between avidin and biotin. Liposomes that had biotin bound to their surface and were labeled with 111In, 67Ga, or 99mTc were administered to mice bearing sarcoma 180, followed by administration of avidin 2 or 4 h later. Avidin initiated liposomal aggregation, resulting in their rapid removal by the reticuloendothelial system. Consequently, their blood level was markedly reduced without any changes in tumor levels. The tumor-to-blood ratio reached about 13 at only 2.5 h after administration of 99mTc-labeled liposomes, versus 1.0 or less without postadministration of avidin. Increased liver accumulation was also observed, but it decreased gradually with time.

Animals↗

PubMed1997

[The efficacy of postural drainage in a case of pulmonary edema following cholecystectomy].

An 81-year-old man underwent percutaneous transluminal gallbladder drainage. As the drain was accidentally removed six days later, he received cholecystectomy. After the operation, he developed hypotension, hypoxemia and ST level depression on ECG. He received artificial ventilation and cathecholamines. His chest CT showed marked pulmonary edema, and total protein of the edema-fluid was 3.3 g.dl-1. These findings suggested permeability pulmonary edema. He received postural drainage of the edema-fluid, and the pulmonary oxygenation was gradually improved. He was weaned from artificial ventilation on the 6th ICU day and discharged the next day.

Aged↗

PubMed1996

Two amine oxidases from Aspergillus niger AKU 3302 contain topa quinone as the cofactor: unusual cofactor link to the glutamyl residue occurs only at one of the enzymes.

Amine oxidases (EC 1.4.3.6) from Aspergillus niger, AO-I (2 x 75 kDa) and AO-II (80 kDa), were examined to determine the cofactor structure. Inactivated with p-nitrophenylhydrazine, they showed absorption and fluorescence spectra similar to those published for other copper amine oxidases and to topa hydantoin p-nitrophenylhydrazone. After digestion by thermolysin and pronase, cofactor peptides were purified by HPLC and sequenced. For thermolytic peptides, a typical topa consensus sequence, Asn-X-Glu-Tyr, was obtained for AO-II, although in case of AO-I it overlapped with Val-Val-Ile-Glu-Pro-Tyr-Gly. For pronase peptides of AO-I, only the latter sequence was obtained. NMR and mass spectroscopy confirmed the residue X as topa p-nitrophenylhydrazone in AO-II and revealed the presence of a residue Z attached to the Glu in the peptide Val-Val-Ile-Glu(Z)-Pro of AO-I. This residue was separated from the peptide by hydrolysis and identified as a product derived from topa quinone. The data, together with amino-acid sequence of AO-I, confer strong evidence for topa quinone as the cofactor, bound in the typical consensus sequence. Raman spectra of the p-nitrophenylhydrazone derivative of AO-I and its pronase peptide showed essentially the same peaks matching to a model compound for topa p-nitrophenylhydrazone. However, there may exist an unusual ester link between the topa-404 and Glu-145 in the native enzyme.

Amine Oxidase (Copper-Containing)↗

PubMed1996

Two distinct quinoprotein amine oxidases are induced by n-butylamine in the mycelia of Aspergillus niger AKU 3302. Purification, characterization, cDNA cloning and sequencing.

Two distinct quinoprotein amine oxidases were found in Aspergillus niger mycelia grown on n-butylamine medium and purified using chromatographic techniques. The respective enzymes were termed AO-I, which had already been isolated, and AO-II, a new enzyme found in this study. HPLC indicated that their molecular masses are 150 kDa and 80 kDa, respectively. On SDS/PAGE, the enzymes gave a similar but distinct mobility, which corresponds to 75 kDa for the subunit dimeric AO-I and 80 kDa for monomeric AO-II. The absorption spectra of both enzymes were different from each other; the absorption maxima in the visible region were at 490 nm for AO-I and 420 nm for AO-II. The enzymes showed positive quinone staining, comparable substrate specificity, and sensitivity to inhibitors typical for copper/topa quinone-containing amine oxidases, but they had different copper contents and also differed in their N-terminal sequences. Their peptide maps showed almost identical patterns, with the exception of two additional bands for AO-II. Among the peptides obtained from digestion of AO-II, peptides with sequences corresponding to the N-terminal part of AO-I were detected. Polyclonal antibodies raised against AO-I and AO-II recognized both enzymes, but with different specificities. Using precipitation with AO-I, the antibody prepared against AO-II was purified and was shown to be specific only for AO-II. The cDNA of AO-I was cloned and sequenced. A highly conserved tetrapeptide sequence, Asn-Tyr-Glu-Tyr, was identified in which the first tyrosine residue (Tyr404) that could be converted to topa quinone was present in the 670-residue deduced amino acid sequence. Northern blot analysis indicated that AO-I was highly expressed in A. niger grown on n-butylamine as a single nitrogen source. Genomic Southern blot analysis confirmed that both enzymes are likely to be encoded by the same gene.

Amine Oxidase (Copper-Containing)↗

PubMed1996

Function of multiple heme c moieties in intramolecular electron transport and ubiquinone reduction in the quinohemoprotein alcohol dehydrogenase-cytochrome c complex of Gluconobacter suboxydans.

Alcohol dehydrogenase (ADH) of acetic acid bacteria functions as the primary dehydrogenase of the ethanol oxidase respiratory chain, where it donates electrons to ubiquinone. ADH is a membrane-bound quinohemoprotein-cytochrome c complex which consists of subunits I (78 kDa), II (48 kDa), and III (14 kDa) and contains several hemes c as well as pyrroloquinoline quinone as prosthetic groups. To understand the role of the heme c moieties in the intramolecular electron transport and the ubiquinone reduction, the ADH complex of Gluconobacter suboxydans was separated into a subunit I/III complex and subunit II, then reconstituted into the complex. The subunit I/III complex, probably subunit I, contained 1 mol each of pyrroloquinoline quinone and heme c and exhibited significant ferricyanide reductase, but no Q1 reductase activities. Subunit II was a triheme cytochrome c and had no enzyme activity, but it enabled the subunit I/III complex to reproduce the Q1 and ferricyanide reductase activities. Hybrid ADH consisting of the subunit I/III complex of G. suboxydans ADH and subunit II of Acetobacter aceti ADH was constructed and it had showed a significant Q1 reductase activity, indicating that subunit II has a ubiquinone-binding site. Inactive ADH from G. suboxydans exhibiting only 10% of the Q1 and ferricyanide reductase activities of the active enzyme has been isolated separately from active ADH (Matsushita, K., Yakushi, T., Takaki, Y., Toyama, H., and Adachi, O (1995) J. Bacteriol. 177, 6552-6559). Using these active and inactive ADHs and also isolated subunit I/III complex, we performed kinetic studies which suggested that ADH contains four ferricyanide-reacting sites, one of which was detected in subunit I and the others in subunit II. One of the three ferricyanide-reacting sites in subunit II was defective in inactive ADH. The ferricyanide-reacting site remained inactive even after alkali treatment of inactive ADH and also after reconstituting the ADH complex from the subunits, in contrast to the restoration of Q1 reductase activity and the other ferricyanide reductase activities. Thus, the data suggested that the heme c in subunit I and two of the three heme c moieties in subunit II are involved in the intramolecular electron transport of ADH into ubiquinone, where one of the two heme c sites may work at, or close to, the ubiquinone-reacting site and another between that and the heme c site in subunit I. The remaining heme c moiety in subunit II may have a function other than the electron transfer from ethanol to ubiquinone in ADH.

Acetobacter↗