Biomedical subjects

R Iwata

Publications and source records attributed to R Iwata.

At least 55 records · Page 3Linked to original sources

PubMed1996

Analysis of plasma metabolites during human PET-studies with three receptor ligands, [11C]YM-09151-2, [11C]doxepin and [11C]pyrilamine.

Carbon-11 labeled metabolites in human plasma were analyzed by high-performance liquid chromatography during positron emission tomography (PET) studies using the dopamine D2 ligand [11C]YM-09151-2 as well as the histamine H1 ligands [11C]doxepin and [11C]pyrilamine. For all the three tracers, blood clearance of the radioactivity was extremely rapid after an i.v. injection. The plasma protein-binding of [11C]YM-09151-2 and [11C]doxepin had protective effects upon the metabolic alteration of the ligands, whereas [11C]pyrilamine was free from the protein-binding and immediately degraded. The degradation of [11C]doxepin was more rapid in epileptic patients on medication than in normal subjects. These results indicate that analysis of metabolites in the plasma is necessary to determine the accurate arterial input function for quantitative PET measurement.

Adult↗

PubMed1996

Direct determination of plasma endothelin-I by chemiluminescence enzyme immunoassay.

A highly sensitive sandwich-type chemiluminescence enzyme immunoassay for plasma endothelin-I (ET-1), involving no extraction steps, has been developed. Two populations of polyclonal antibodies were used in the present study: One is specific to the C-terminus of the endothelin family of peptides; the other, a Fab' fragment against the N-terminal core region of ET-1, is coupled with horseradish peroxidase (HRP). Labeled HRP activity was measured by using an enhanced chemiluminescence reaction of luminol/hydrogen peroxide. The assay was sensitive enough to detect 0.5 ng/L (0.05 pg/well) of plasma ET-1 and had no significant cross-reactivities with other related peptides, including endothelin-3 and the endothelin precursor peptide, big ET-1. Reliability of the assay was confirmed by comparison with an extraction-based procedure and a commercial kit.

Adult↗

PubMed1996

[Development of simple on-line [oxygen-15]water infuser].

A [15O]water production and infusion system was newly developed for blood flow study with positron emission tomography. The system utilizes a electrostatic cooling unit to liquify [15O]vapor in a coiled plastic tube. Labeled [15O]water is collected into an infusion syringe by a wash of the trapping tube with saline. The system is simple and efficient; the recovery rate of [15O]water is over 90% at 10 degrees C of cooling temperature.

Cerebrovascular Circulation↗

PubMed1996

PET study of cerebral glucose metabolism and fluorodopa uptake in patients with corticobasal degeneration.

We measured cerebral glucose utilization and fluorodopa metabolism in the brain of patients with corticobasal degeneration using position emission tomography. The clinical pictures are distinctive, comprising features referable to both cerebral cortical and basal ganglionic dysfunctions. Brain images of glucose metabolism can demonstrate specific abnormalities with a marked asymmetry in the parietal cortex (the primary motor and sensory cortex and the lateral parietal cortex), the thalamus, the caudate nucleus and the putamen of the dominantly affected hemisphere related to clinical symptoms in six patients. [18F]dopa uptake also reduced in an asymmetric pattern, both the caudate nucleus and the putamen in four patients. This unique combination study measuring both cerebral glucose utilization and fluorodopa metabolism in the nigrostriatal system can provide efficient information about the dysfunctions which are correlated with individual clinical symptoms.

Aged↗

PubMed1996

Re-evaluation of myocardial FDG uptake in hyperglycemia.

UNLABELLED: Myocardial [18F] fluorodeoxyglucose (FDG) uptake depends on several metabolic variables in vivo. The effect of different levels of experimentally induced hyperglycemia on myocardial FDG uptake was examined. METHODS: FDG uptake was studied in young Donryu rats 1 hr after intravenous injection under various pretreatments that increased serum glucose levels. Serum samples were analyzed for glucose, insulin and free fatty acids. Myocardial distribution of FDG was examined with autoradiography. RESULTS: Administration of glucose (n = 42), triiodothyronine (n = 7), epinephrine (n = 7), dehydroascorbic acid (n = 5) and 4 mg streptozotocin (Szt, n = 10) increased glucose levels to 120-200 mg/dl. Dexamethasone (Dex, n = 34) and 6 mg Szt (n = 6) increased glucose levels to 200-450 mg/dl. Myocardial FDG uptake increased proportionately with increases in serum glucose level up to 200 mg/dl. In severe hyperglycemia (serum glucose: 200-450 mg/dl), however, the FDG uptake decreased and did not correlate with blood glucose level. A study of fractional FDG uptake calibrated by the arterial FDG curve confirmed the same results. Heterogeneous distribution of FDG was observed in the myocardium, both in fasting and in severe hyperglycemic conditions. The pattern of FDG uptake by skeletal muscles was similar to that of the myocardium, although the uptake was lower than that in the myocardium. Changes in insulin and free fatty acids levels could not explain the FDG uptake pattern in severe hyperglycemia. Blood FDG uptake level remained constant regardless of glucose level. CONCLUSION: Hyperglycemia induced a biphasic pattern of myocardial FDG uptake, common with skeletal muscles. The understanding of myocardial FDG uptake characteristics and their dependence on blood glucose is helpful in interpreting myocardial FDG-PET images.

Animals↗

PubMed1995

Stable and general-purpose chemiluminescent detection system for horseradish peroxidase employing a thiazole compound enhancer and some additives.

A stable and highly sensitive chemiluminescent detection system for horseradish peroxidase (HRP)/luminol/hydrogen peroxide using a newly designed thiazole compound enhancer has been established. Some additives for the chemiluminescent reaction were explored to overcome some defects of the reaction such as rapid decay and high background of light emission. Recrystallization of luminol and the addition of several detergents into the reacting solution were effective to increase specific light emissions. The addition of skim milk into the reacting solution reduced the background. Consequently, skim milk combined with a detergent increased the signal to noise ratio about 20 times compared with the reactions in the absence of both additives. The optimal concentration of enhancer and the addition of egg albumin stabilized the emission. In the new method, 6x 10(-18) mol of HRP was detectable. This would be the most sensitive enhanced chemiluminescent detection system for HRP. Furthermore, we could detect picogram per milliliter (10(-17) mol) concentrations of a trace component in biological materials such as endothelin-1 by employing this reaction.

Endothelins↗

PubMed1995

Positron emission tomography (PET) study of the alterations in brain distribution of [11C]methamphetamine in methamphetamine sensitized dog.

[11C]Methamphetamine ([11C]MAP) was synthesized by an automated on-line [11C]methylation system for positron emission tomography (PET) study. We newly produced a MAP sensitized dog by repeated MAP treatment and studied the brain distribution of [11C]MAP in the normal and the MAP sensitized dog. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [11C]MAP in the MAP sensitized brain indicates that subchronic MAP administration causes some functional change in uptake site of MAP.

Animals↗

PubMed1995

Histamine H1 receptor occupancy in human brains after single oral doses of histamine H1 antagonists measured by positron emission tomography.

1. Histamine H1 receptor occupancy in the human brain was measured in 20 healthy young men by positron emission tomography (PET) using [11C]-doxepin. 2. (+)-Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 +/- 4.2% of the averaged values of available histamine H1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Intravenous administration of 5 mg (+)-chlorpheniramine almost completely abolished the binding of [11C]-doxepin to H1 receptors (H1 receptor occupancy: 98.2 +/- 1.2%). 3. Terfenadine, a nonsedative antihistamine, occupied 17.2 +/- 14.2% of the available H1 receptors in the human frontal cortex after its administration in a single oral dose of 60 mg. 4. There was no correlation between H1 receptor occupancy by terfenadine and the plasma concentration of the active acid metabolite of terfenadine in each subject. 5. PET data on human brain were essentially compatible with those on H1 receptor occupancy in guinea-pig brain determined by in vivo binding techniques, although for the same H1 receptor occupancy the dose was less in human subjects than in guinea-pigs. 6. The PET studies demonstrated the usefulness of measuring H1 receptor occupancy with classical and second-generation antihistamines in human brain to estimate their unwanted side effects such as sedation and drowsiness quantitatively.

Administration, Oral↗

PubMed1995

Methionine uptake by tumor tissue: a microautoradiographic comparison with FDG.

UNLABELLED: L-methyl-11C-methionine (11C-Met) and 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) are used for tumor diagnosis and treatment evaluation by PET. In order to examine the role of these tracers in cancer imaging, intratumoral properties of 14C-Met were studied and compared to those of 18F-FDG. METHODS: The distribution of 14C-Met in various cellular elements of two different mouse malignant tumor tissues, MH134 and FM3A, was analyzed serially using microautoradiography within a period of 120 min after injection of the tracer. RESULTS: Carbon-14-Met and 18F-FDG showed different distributions in tumor tissue. Carbon-14-Met uptake by the tumor was mostly by viable cancer cells. The uptake by macrophages and other cellular components was low. The uptake was higher in the highly proliferative tumor but did not reflect protein synthesis. The rapid and slow growing tumors demonstrated that 14C-Met uptake ratio was lower than that of 18F-FDG, reflecting de novo DNA synthesis ratio. CONCLUSION: Carbon-14-Met uptake represents the presence of viable cancer cells. Carbon-11-Met may be suitable for treatment evaluation of individual tumors but not growth rates of different tumors. Fluorine-18-FDG reflects tumor-host immune system reaction and is an excellent tool for pretreatment evaluation of tumors and determination of tumor proliferative activity.

Animals↗

PubMed1995

Automated nurse rostering system for administrative efficiency as a subsystem of a total hospital information system.

After trying a variety of nurse scheduling packages, the Chiba University Hospital chose to develop their own system and implemented it in April 1994. The system is the newest component of their HIS which has been functioning since 1991. The rostering system avails itself of the modern client server technology which has been installed over the past few years.

Hospital Information Systems↗

PubMed1995

Positron emission tomographic study of central histamine H1-receptor occupancy in human subjects treated with epinastine, a second-generation antihistamine.

Histamine H1-receptor occupancy in the human brain was measured in healthy young volunteers by positron emission tomography (PET) using [11C]doxepin. d-Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 +/- 4.2% of the averaged values of available histamine H1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Epinastine, a non-sedative antihistamine, occupied 13.2 +/- 18.5% of the available H1 receptors in the human frontal cortex after its administration in a single oral dose of 20 mg. There was significant correlation between H1 receptor occupancy by epinastine and its plasma concentration in each subject. PET data on the human brain were essentially compatible with those on H1-receptor occupancy in the guinea pig brain as determined by an in vivo binding technique, although for the same H1-receptor occupancy, the dose was less in humans than in guinea pigs. Our PET studies demonstrated that receptor occupancy by a second-generation H1 antagonist, epinastine, was less than 20% of the total H1 receptors, and that the low receptor occupancy was closely related to the low incidence of central side effects.

Adult↗

PubMed1994

Heterogeneous distributions of histamine H3, dopamine D1 and D2 receptors in rat brain.

The changes of the histamine H3 and dopamine D1 or D2 receptor binding sites induced by quinolinic acid treatment were studied in order to discriminate the comparative distribution. This treatment resulted in similar decreases in histamine H3 and dopamine D1 receptor binding sites in the striatum and ipsilateral substantia nigra. Dopamine D2 receptor binding sites were relatively well conserved, whereas H3 receptors decreased considerably. These results suggest that histamine H3 and dopamine D1 receptor binding sites are localized on the striatonigral projection neurones which are together sensitive to quinolinic acid, and that the distributional compartment of dopamine D2 receptor binding sites is quite different from those of histamine H3 and dopamine D1 receptors.

Animals↗

PubMed1994

Assessment of dopamine metabolism in brain of patients with dementia by means of 18F-fluorodopa and PET.

By means of positron emission tomography (PET) and 18F-fluorodopa (FDOPA), a study was initiated to analyze the cerebral dopamine (DA) metabolism of 32 subjects including those with AD/SDAT and vascular dementia (VD, multi-infarct type). A semiautomated irregular ROI drawing routine to identify the striatum was developed that interactively defined the PET threshold pixels referring to the count histograms and location of the corresponding pixels. A comparative study by five examiners showed significant improvement in the area size definition and count linearity particularly for low contrast objects. The graphical plot was employed to calculate the FDOPA influx rate (Ki) for the ROI data with cerebellar radioactivity as an input function. The striatal Ki value was found to be relatively stable and did not show signs of a significant age-related change. The vascular patients had smaller Ki to the striatum than the aged control. Although the mean Ki of AD/SDAT was almost compatible with that of age-matched normals, their Ki was more scattered with higher and lower Ki cases. The multiple regression analysis revealed that the Ki could be predicted by age and the mini-mental state (MMS) performance (r2 = 0.590, p < 0.01 for AD/SDAT, r2 = 0.401, and p < 0.05 for VD). MMS was found to be a more dominant factor than age. We conclude that dopamine metabolism became disturbed as dementia became progressively severe.

Aged↗

PubMed1994

Binding characteristics of a histamine H3-receptor antagonist, [3H]S-methylthioperamide: comparison with [3H](R)alpha-methylhistamine binding to rat tissues.

The release and synthesis of neuronal histamine are regulated by histaminergic autoreceptors named as histamine H3 receptors. The development of radiolabeled histamine H3 antagonists is needed to characterize the binding of antagonists to these receptors. Here we describe the binding characteristics of a new histamine H3-receptor antagonist, [3H]S-methylthioperamide (SMT), to rat tissues, and compare its binding with that of [3H](R)alpha-methylhistamine ((R)alpha MH), a selective histamine H3-receptor agonist. The binding of [3H]SMT to the membranes of rat forebrain was found to be stereoselective, saturable, reversible and temperature-dependent. Saturation binding experiments indicated a single class of high affinity sites for [3H]SMT in forebrain membranes (KD = 2.1 nM, Bmax = 24.3 pmol/g of tissue at 4 degrees C). The Bmax was approximately 3 times that of [3H](R)alpha MH binding to rat forebrain membranes (KD = 2.5 nM, Bmax = 7.3 pmol/g of tissue at 25 degrees C). Autoradiographic images of [3H]SMT binding in the brain were essentially the same as those of [3H](R)alpha MH. [3H]SMT also bound appreciably to peripheral tissues (the liver, adrenal, stomach, ileum, kidney, lung and bladder), whereas the [3H](R)alpha MH bindings to these peripheral tissues were negligible. These results indicate that [3H]SMT binds to H3 receptors primarily in the central nervous system, and that it also has high affinity toward non-H3 receptors, probably hemoproteins, in peripheral tissues.

Animals↗

PubMed1994

[A case of hepatocellular carcinoma with lumbar bone metastasis with high uptake of 18F-fluorodeoxygalactose in PET].

18F-fluorodeoxygalactose (18FDGal) is a tracer for the evaluation of galactose metabolism in the tissue. PET with 18FDGal was performed in a hepatoma (HCC) patient with lumbar bone metastasis. The image at 45 min after i.v. injection of 18FDGal demonstrated very high uptake by the bone metastasis with tumor-to-surrounding normal tissue ratio of 36. The tumor uptake expressed by differential absorption ratio was much higher than that in the cirrhotic liver and kidney. The result indicated that the HCC maintained high activity of galactose metabolism and rises the potential of this tracer for detecting extrahepatic metastases of HCC using PET.

Carcinoma, Hepatocellular↗

PubMed1993

Brain tumor accumulation and plasma pharmacokinetic parameters of 2'-deoxy-5-18F-fluorouridine.

Using positron emission tomography and radio-high performance liquid chromatography, the accumulation of 2'-deoxy-5-18F-fluorouridine in the brain tumors and plasma pharmacokinetic parameters were investigated in 20 patients. High accumulation of the tracer in high grade gliomas and meningiomas and very rapid degradation of the tracer in the plasma were found. Very large variations were observed in both tumor accumulation and pharmacokinetic data. The tumor accumulation, however, did not correlate with any of the plasma pharmacokinetic parameters: area under the plasma concentration-time curve, mean residence time, total body clearance and steady-state volume of distribution. The results suggest that the accumulation of the tracer reflects the metabolic activity of the brain tumor tissues and that the effect of the rapid metabolic change in the tracer in the plasma on the tumor accumulation may be minor.

Adult↗

PubMed1993

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↗

PubMed1993

Helical computed tomography scanning of the thorax and abdomen.

We applied helical CT to examinations of the abdomen and thorax. Scanning was performed continuously while the couchtop of the CT scanner was shifted at a constant speed. The entire lung field could be scanned during a single holding of the breath when the couchtop speed was 20 mm/s. Tumors as small as 3 mm were detected. The diagnostic detectability and accuracy of helical CT were far superior to those of conventional chest radiography. During abdominal examination, the target organ could be scanned at any specified phase (preferably arterial) during the injection of contrast medium. We detected very small hepatic tumors which could not be detected by conventional CT. Helical CT produced continuous data, which was reconstructed to display three-dimensional images. Helical CT could be used in mass screening for the detection of early lung cancer and in computer-aided diagnosis.

Abdominal Neoplasms↗