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Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 973 records · Page 54Linked to original sources

Metabolic imaging in hemianopsia using positron emission tomography with 18F-deoxyfluoroglucose.

To evaluate the usefulness of metabolic mapping by positron emission tomography using 18F-deoxyfluoroglucose as a tracer in the diagnosis of hemianopsia, we examined eight patients who had had cerebrovascular accident, and four controls. Neuro-ophthalmologic examination disclosed hemianopsia in five and incomplete hemianopsia in three patients; computed tomography showed low-density areas in four patients; and nuclear magnetic resonance imaging demonstrated a prolonged T2 area in five patients. The cerebral metabolic rate for glucose without visual stimulation in the visual cortex was 7.4 +/- 1.0 mg/min/100 g of brain without interhemispheric asymmetry. Light stimulation increased cerebral metabolic rate for glucose in the visual cortex of the nonaffected hemisphere and decreased it in the affected hemisphere. Asymmetry in the metabolic rate in the posterior medial occipital cortex in complete hemianopsia was 22% 12% (P less than .01).

Adult↗

Immunohistochemical demonstration of histamine N-methyltransferase-like structures in rat kidney.

Histamine N-methyltransferase (S-adenosylmethionine: histamine N-methyltransferase, E.C. 2.1.1.8) was purified to homogeneity from rat kidney, and antibody was raised against it in guinea pigs. The antibody immunoprecipitated histamine N-methyltransferase. Immunofluorescent histochemical studies with anti-histamine N-methyltransferase antibody as the first antibody and goat anti-guinea pig IgG conjugated with fluorescein isothiocyanate as the second, showed the presence of immunoreactive structures in the proximal tubules of rat kidney. The brain showed no immunoreaction with the antibody.

Animals↗

Use of 11C-triphenylmethylphosphonium for the evaluation of membrane potential in the heart by positron-emission tomography.

The membrane potential in cells can be estimated by electrophysiological techniques and biomedical methods using lipophilic cations labelled with 14C. However, these techniques cannot be applied to the human heart. In this study a lipophilic cation, triphenylmethylphosphonium (TPMP), was labelled with carbon-11 with the purpose of investigating its suitability for the estimation of membrane potential in vivo. A biodistribution study in mice and rats showed significant uptake of the cation in the heart a few minutes after IV injection which remained constant for 60 min. In vivo study by positron-emission tomography showed that after IV injection of 11C-TPMP in the dog, activity rose almost immediately in the myocardium and then remained constant for 60 min. A rapid injection of KCl (greater than 40 mg/kg) 20 min after injection of 11C-TPMP led to an instantaneous fall in myocardial 11C-TPMP concentration. Membrane potential (delta psi), calculated from the TPMP distribution ratio between intracellular and plasma water space by the Nernst equation, was estimated at -148.1 +/- 6.0 mV for the dog heart. This value reflected both cell membrane potential and mitochondrial membrane potential and, thus, the energy state of the myocardial cells.

Animals↗

2-Deoxy-2-[18F]fluoro-D-galactose: a new tracer for the measurement of galactose metabolism in the liver by positron emission tomography.

We prepared 2-deoxy-2-[18F]fluoro-D-galactose as a potential radiopharmaceutical for liver imaging and for the assessment by positron emission tomography of regional metabolic function of the liver. In biodistribution studies of rats, the liver uptake of the compound was very high, almost reaching a plateau (6.33% dose/g) at 30 min and remaining constant until 120 min. This high uptake was reduced by simultaneous administration of D-galactose, but D-glucose had no effect. The compound was much less concentrated in the liver that had been damaged by CCl4 treatment. Positron imaging of a rabbit liver showed a remarkable uptake of the compound with a high liver-to-blood ratio. The high concentration in the liver was also reduced by the administration of D-galactose. These data suggest that the compound was trapped in the liver by a metabolic process and could be used for the measurement by positron emission tomography of galactose metabolism in the liver.

Animals↗

Assessment of radiotherapeutic effects on experimental tumors using 18F-2-fluoro-2-deoxy-D-glucose.

The purpose of this study is to evaluate the effect of tumor volume and radiotherapy on the uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG). The tumor models used were mouse mammary carcinoma MM48, FM3A, and rat hepatoma AH109A. Results were expressed as an 18FDG uptake ratio. This was the ratio of irradiated tumor uptake of 18FDG to unirradiated tumor uptake. The total tumor uptake was expressed as 18FDG uptake ratio multiplied by relative tumor volume. Following 20 Gy irradiation of the radioresistant tumor (MM48), the 18FDG uptake ratio was found to be unchanged, whereas in radiosensitive tumors (FM3A) the 18FDG uptake ratio was 0.37, the relative tumor volume was 0.31, and the calculated total tumor uptake was 0.11 on the eighth day after irradiation. The total tumor uptake was lower than the relative tumor volume. AH109A began to regrow after ten Gy irradiation, accompanied by elevated uptake of 18FDG on the seventh day. These results suggest that the 18FDG uptake by tumor is a good marker of radiotherapeutic effects as well as relapses of cancers and is more sensitive than morphological methods.

Animals↗

S-adenosyl-L-methionine and lead intoxication: its therapeutic effect varying the route of administration.

A comparative study on the effect of oral and subcutaneous (sc) or intravenous (iv) administration of S-adenosyl-L-methionine (SAM) in lead poisoning was carried out. SAM was given daily sc (20 mg/kg) and orally (80 mg/kg) to acute lead-intoxicated mice for 20 days. Chronic lead-poisoned patients received SAM, administered intravenously at a daily dose of 12 mg/kg or orally at a dose of 25-30 mg/kg. Independent of the method of administration in either animals or patients, GSH concentration in reduced lead intoxication was increased after SAM dosing. Corresponding blood lead content rapidly decreased and a significant recovery of hepatic and erythrocytic delta-aminolevulinate dehydratase (ALA-D), initially reduced, was clearly produced in the groups receiving SAM, although the response was slightly slower when SAM was given orally. It was found that the bulk of body lead burden was excreted in the feces, showing a peak within the first 24-48 hr and being much greater in animals treated with SAM. In these cases, urinary lead excretion was very low. Lead ALA-D inhibition was also evidenced by elevated urinary excretion of delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and porphyrins. During treatment, precursors and porphyrins elimination declined, reaching normal levels soon after therapy ended. A good correlation between the recovery of both GSH levels and ALA-D activity and decreased lead content was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cerebellar cyclic nucleotides and the development of convulsion, with reference to the anticonvulsant activity of diazepam.

Dibutyryl cyclic GMP (DbcGMP) or dibutyryl cyclic AMP (DbcAMP) given to rats intracerebellarly in a dose of 200 nmol/head produced electroencephalographic convulsive changes. Intracerebellar (i.c.) administration of lower doses (100 nmol/head) of DbcGMP and DbcAMP and 200 nmol/head of norepinephrine (NE) and glutamate (Glu) facilitated the pentylenetetrazol (PTZ)-induced convulsions. Diazepam (100 nmol/head, i.c.) suppressed the PTZ-induced convulsions. GABA (400 nmol/head, i.c.) did not affect the PTZ-induced convulsions. These results suggest that DbcGMP, DbcAMP and Glu inhibit seizure control mechanisms in the cerebellum, and that one of the sites of the anticonvulsant action of diazepam is located in the cerebellum.

Animals↗

DIDS, an anion transport blocker, modulates ivermectin-induced enhancement of benzodiazepine receptor binding in rat brain.

Ivermectin enhancement of [3H]diazepam binding was abolished by pretreatment of membranes with 0.05% Triton X-100, whereas GABA-induced enhancement was not changed after this treatment. Ivermectin enhancement was neither affected by picrotoxinin nor dependent on the chloride ion. 4,4'-Diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) dose-dependently reduced [3H]diazepam binding enhanced by 10(-6) M ivermectin, without affecting the basal specific binding. The effects of DIDS were derived from reduction of increased binding affinity of benzodiazepine receptors by ivermectin, but were not dependent on chloride ion in the assay medium. DIDS inhibited GABA- and pentobarbital- but not chloride ion-induced enhancement of [3H]diazepam binding.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Effects of tizanidine, a centrally acting muscle relaxant, on motor systems.

Effects of tizanidine were studied with special reference to the effect on motor systems. The drug effectively reduced the intercollicular decerebrate rigidity and gamma-activity indirectly recorded from muscle spindle afferent discharges without showing the direct inhibitory effect on muscle spindles in rats. The drug dose-dependently inhibited the phasic responses of alpha-rigidity in anemic decerebrate rats without showing marked inhibition of the tonic response. Tizanidine effectively depressed the crossed extensor reflex in chicks and depressed mono- and polysynaptic reflex potentials in rats; dorsal root reflex was increased transiently. Tizanidine had no effect on the neuromuscular junction in rats and [3H]diazepam binding in rat brain membrane. It is suggested that the depression by tizanidine of gamma-system and spinal reflexes contribute to muscle relaxation and anti-spastic effects and that mechanisms of action are different from those of other centrally acting muscle relaxants such as mephenesin and benzodiazepines.

Animals↗

Brain stem involvement in the effects of chlorpromazine on the monosynaptic reflex of the rat lumbar spinal cord.

The brain stem areas involved in the inhibitory effect of chlorpromazine (CPZ) on the monosynaptic reflex (MSR) in the lumbar spinal cord of rats were investigated following brain stem transection and focal thermo-lesioning. Transection of the medulla oblongata markedly reduced the effect of CPZ, while transection in the mid-brain or more anterior level did not alter the effect of CPZ. With regard to focal lesions at various sites of the brain stem, lesioning of the medial portion of the medulla oblongata most effectively attenuated the MSR inhibition by CPZ and also attenuated the MSR inhibition induced by phenoxybenzamine. Bilateral lesioning of the locus coeruleus did not attenuate the MSR inhibition by CPZ. These results suggest that the pathway involved in the inhibitory effect of CPZ on the MSR originates in the pons and passes through the medial portion of the medulla oblongata, and that the coerulo-spinal pathway is not the major pathway involved in the effect of CPZ.

Animals↗

Enkephalin but not morphine modulates the motor activity in the frog spinal cord in vitro.

In the isolated frog spinal cord, methionine-enkephalin (ME, up to 3 X 10(-5) M) hyperpolarized the resting ventral and dorsal root potentials. These hyperpolarizations remained even under Ca2+-free conditions. ME depressed the fast component of the electrically stimulated spinal reflex and enlarged the following depolarizing component. Morphine (10(-4) M) had no apparent ME-like effects. ME may directly and indirectly affect the motoneuron and modulate the spinal motor activity in the frog spinal cord.

Animals↗

Effects of dietary proteins on lipogenic enzymes in rat liver.

When fasted rats were fed fat-free diets containing various sources of protein for 3 d, the activities of liver glucose-6-phosphate dehydrogenase, malic enzyme, acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in rats fed soybean protein or gluten than in those fed casein or fish protein. Since malic enzyme mRNA activity was not low in the soybean protein-fed animals, the translation of malic enzyme appears to be suppressed by dietary soybean protein. The incorporation of tritiated water into liver fatty acids was significantly lower in animals fed soybean protein than in those fed casein. The triglyceride levels in plasma and especially in liver were also lower in the groups fed soybean and gluten than in the groups fed casein and fish. In addition, when dietary soybean protein was replaced with amino acids to simulate casein or soybean protein, the effects on the levels of lipogenic enzymes were still found but were not as great. Thus, some effects can be ascribed to the protein itself and some to the amino acid composition of the diet.

Acetyl-CoA Carboxylase↗

Ketanserin potentiates the prejunctional inhibitory effect of 5-hydroxytryptamine on rat vas deferens.

5-Hydroxytryptamine (5-HT) slightly inhibited the twitch contractions of rat vas deferens caused by single pulse field stimulation at 0.1 Hz. The inhibitory effect of 5-HT was much less in the epididymal portion than in the prostatic portion of the vas deferens. Ketanserin potentiated the prejunctional inhibitory effect of 5-HT and attenuated its stimulatory effect. This potentiation was observable only in the epididymal portion, of the vas deferens. Cyproheptadine and mianserin, but not methysergide, had essentially similar potentiating effects to those of ketanserin. These results suggest that the 5-HT receptor that mediates prejunctional inhibition is not of the 5-HT2 type, and that ketanserin acts by suppressing the 5-HT-induced stimulatory effect, which is possibly mediated by a postjunctional 5-HT2 receptor, thus unmasking the inhibitory effect of 5-HT.

Animals↗

Orbital tumor diagnosis by positron emission tomography using 18F-fluorodeoxyuridine.

The distribution of 18F-labeled 5-fluoro-2'-deoxyuridine (18F-FdUrd) in orbital tissue, tumor and aseptic inflammation was examined in rats. The distribution in paraorbital structures, other than bone, was low. The tumor-to-organ ratios were sufficient for tumor imaging by positron emission tomography (PET). Positron emission tomography with 18F-FdUrd clearly showed the experimental orbital VX-2 tumor in rabbits. The difference between the experimental orbital tumor and croton oil-induced aseptic inflammation or a normal orbit was apparently established in the PET image with slow and fast clearance of radioactivity, respectively.

Animals↗