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T Suhara

Publications and source records attributed to T Suhara.

83 records · Page 5Linked to original sources
PubMed1991

Age-related changes in human D1 dopamine receptors measured by positron emission tomography.

The effects of age on the binding parameters of 11C-SCH23390, the highly selective ligand for central D1 dopamine receptors, at specific binding sites in the brain were studied. Seventeen healthy male volunteers (20-72 years old) participated. Regional radioactivity in the brain was followed for 40 min by positron emission tomography (PET). A high accumulation of radioactivity was observed in the striatum and there was a conspicuous accumulation in the neocortex. A two-compartment model was used to obtain quantitative estimates of rate constants of association (K3) and dissociation (k4). The binding potential (k3/k4) of the dopamine D1 receptors in the striatum and frontal cortex decreased by 35% and 39%, respectively, with age. The value of k3 decreased by 58% in the striatum and 83% in the frontal cortex, whereas the value of k4 decreased by 35% in the striatum and 72% in the frontal cortex with age.

Adult↗
PubMed1991

Swim stress alters in vivo binding of [3H]N-methylspiperone.

The effect of swim stress on the in vivo binding of [3H]N-methylspiperone in the striatum of the mouse was investigated. Mice were forced to swim for 5 min at 18 degrees C and the time course of radioactivity in the striatum and cerebellum, following intravenous injection of [3H]N-methylspiperone was measured. The ratio of radioactivity in the striatum to that in the cerebellum was plotted as a function of time for the estimation of in vivo binding to dopamine D2 receptors. Immediately after the swim stress, a significant decrease in binding to D2 receptors in vivo was observed. Neither the KD nor Bmax determined by in vitro binding were altered by swim stress. The time course of the changes in binding, within a 24 hr period, following the swim stress was also studied and a rapid reversal of binding, within 1 hr after the swim stress was observed. In vivo binding of [3H]N-methylspiperone in the cerebral cortex, which appeared to involve serotonin receptors, as well as D2 receptors, was not significantly altered by the swim stress. A saturation study of in vivo binding indicated that the decreases in binding to D2 receptors, due to swim stress, were primarily caused by changes in the apparent affinity rather than in the number of binding sites available in vivo. These results support the hypothesis that micro-environmental factors, including the diffusion barrier to the synapse, might be altered by swim stress.

Animals↗
PubMed1991

[Effect of aging on in vivo binding of 11C-N-methylspiperone in living human frontal cortex].

Reduced in vivo binding of 11C-N-methylspiperone (NMSP) with age in the living human frontal cortex was demonstrated, with positron emission tomography (PET). Eleven normal male volunteers (22 to 72 years old) were assessed. The uptake of 11C-NMSP in the frontal cortex peaked 7-15 min after intravenous injection, and then gradually decreased until the end of this study. On the other hand in the cerebellum, the uptake of 11C-NMSP peaked 10 min and rapidly declined. We analyzed the data using a three compartment model and determined rate constants k3 and k4. And the binding potential of receptors was estimated as the ratio of k3 (association rate constant) to k4 (dissociation rate constant) value. The k3 and k4 values were calculated from nonlinear regression, given by the set of parameter values that minimized the deviation between the measured kinetics and model prediction. As an input function, we used the radioactivity in the cerebellum. A significant reduction in BP with age was observed. Though both k3 and k4 values were decreased with age, this decrease of BP was found to be mainly due to the reduced k3 values. These results indicated that numbers of binding sites (Bmax) of serotonin S2 receptors in frontal cortex might be decreased with age.

Adult↗
PubMed1990

Effect of desipramine on dopamine receptor binding in vivo.

Effect of desipramine (given i.p. 30 min prior to the tracer injection) on the in vivo binding of 3H-SCH23390 and 3H-N-methylspiperone (3H-NMSP) in mouse striatum was studied. The ratio of radioactivity in the striatum to that in the cerebellum at 15 min after i.v. injection of 3H-SCH23390 or 45 min after injection of 3H-NMSP were used as indices of dopamine D1 or D2 receptor binding in vivo, respectively. In vivo binding of D1 and D2 receptors was decreased in a dose-dependent manner by acute treatment with desipramine (DMI). A saturation experiment suggested that the DMI-induced reduction in the binding was mainly due to the decrease in the affinity of both receptors. No direct interactions between the dopamine receptors and DMI were observed in vitro by the addition of 1 mM of DMI into striatal homogenate. Other antidepressants such as imipramine, clomipramine, maprotiline and mianserin also decreased the binding of dopamine D1 and D2 receptors. The results indicated an important role of dopamine receptors in the pharmacological effect of antidepressants.

Animals↗
PubMed1990

[A case of metastatic malignant melanoma of the stomach treated by a surgical operation].

A metastatic malignant melanoma of the stomach is not a disease of rate occurrence, but reports of melanomas that were clinically diagnosed and were treated by a surgical operation are rare. The case presented is a 73-year-old woman, who underwent an excision of a malignant melanoma of the left sole in 1981. Subsequently, she had a subcutaneous metastasis of a melanoma three times and was treated by a resection and immunochemotherapy. In January, 1988, an X-ray examination of stomach revealed a giant elevated lesion, and an endoscopic examination of the stomach revealed a black pigmented tumor with ulceration. A biopsy taken from the tumor confirmed the diagnosis of a malignant melanoma. Thus, she was given a total gastrectomy. Reports in the Japanese literature of metastatic malignant melanomas of the stomach diagnosed while the patient was still living amount to 11 cases. Of this number, 3 patients were given a surgical operation. Further, these 3 patients lived longer than the non-surgically treated cases and had a better quality of remaining life.

Aged↗
PubMedDate not supplied

PET study of the M1-agonists [11C]xanomeline and [11C]butylthio-TZTP in monkey and man.

Xanomeline, a substituted TZTP, is a new M1 selective muscarinic agonist in clinical trials for Alzheimer's disease. The brain uptake of [11C]xanomeline and the analog [11C]butylthio-TZTP was examined by positron emission tomography (PET). Radioactivity accumulated most markedly in the neocortex and the striatum. Pharmacological characterization in vitro and in cynomolgus monkeys in vivo by PET indicated specific [11C]butylthio-TZTP binding to muscarinic receptors and to sigma-1 recognition sites. More than 5% of the radioactivity was in the human brain 5 min after i.v. injection of [11C]xamomeline or [11C]butylthio-TZTP. This high brain uptake may be clinically advantageous in the sense that substituted TZTP may induce central muscarinic agonist effects at a dose level for which there is a low risk of peripheral side-effects.

Adult↗