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H Tsukada

Publications and source records attributed to H Tsukada.

At least 73 records · Page 4Linked to original sources

Synthesis and lateral root-inducing activity of novel N-substituted-2-piperidones with a 1,4-benzodioxan ring.

Novel N-substituted-2-piperidones with a 1,4-benzodioxan ring were prepared and evaluated for their activity to induce lateral roots in lettuce seedlings. Compounds were obtained by aldol condensation of the lithium enolate of N-substituted-2-piperidones with 1,4-benzodioxan-6-carbaldehyde. Of the series compounds tested, N-cinnamyl-3-[1-(1,4-benzodioxan-6-yl)-1-hydroxymethyl]-2-piperidone (2e) had the highest activity. In seedlings treated with 10 ppm of 2e, all of the primary roots formed lateral roots. Only erythro-2e showed lateral root-inducing activity, while threo-2e was inactive.

Dioxanes↗

Diagnostic accuracy of CT-guided automated needle biopsy of lung nodules.

OBJECTIVE: The purpose of this study was to determine the factors influencing diagnostic accuracy in CT-guided automated needle biopsies of lung nodules. SUBJECTS AND METHODS: One hundred thirty-eight consecutive CT-guided automated needle biopsy procedures were performed in 123 patients (124 pulmonary nodules). Factors for diagnostic accuracy were evaluated through analysis of the procedures, which were classified into a success group (true-positive and true-negative) and a failure group (false-positive and false-negative). RESULTS: Final diagnoses were 81 malignant lesions (91 biopsies) and 43 benign lesions (47 biopsies). More than two CT-guided biopsies were performed for 13 lesions. Seventy lesions were true-positive, 44 were true-negative, three were false-positive, and 21 were false-negative. The overall diagnostic accuracy was 82.6%. The sensitivity for malignancy and specificity for benign lesions were 76.9% and 93.6%, respectively. Positive and negative predictive values were 95.9% and 67.7%, respectively. Lesion size was a significant factor contributing to diagnostic accuracy (p = 0.014). Mean diameters of lesions (+/-SD) in the success and failure groups were 24.1+/-12.4 mm and 17.6+/-7.8 mm, respectively. For lesions 6-10 mm in diameter, diagnostic accuracy was 66.7%; for lesions 11-20 mm in diameter, 78.9%; for lesions 21-30 mm in diameter, 86.7%; for lesions 31-50 mm in diameter, 93.3%; and for lesions 51-70 mm in diameter, 100%. CONCLUSION: Lesion size was a determining factor in diagnostic accuracy. Diagnostic accuracy decreased in proportion to the decrease in the lesion diameter.

Adult↗

Improvement in cerebral blood flow and metabolism following subarachnoid hemorrhage in response to prophylactic administration of the hydroxyl radical scavenger, AVS, (+/-)-N,N'-propylenedinicotinamide: a positron emission tomography study in rats.

OBJECT: The hydroxyl radical scavenger (+/-)-N,N'-propylenedinicotinamide (AVS) has been shown to ameliorate the occurrence of vasospasm following experimental subarachnoid hemorrhage (SAH) and to reduce the incidence of delayed ischemic neurological deficits (DINDs) in patients with SAH. The authors investigated whether prophylactic administration of AVS could improve cerebral blood flow (CBF) and cerebral glucose utilization (CGU) following SAH in rats. METHODS: Anesthetized rats were subjected to intracisternal injection of blood (SAH group) or saline (control group). Either AVS (1 mg/kg/min) or saline (vehicle group) was continuously injected into the rat femoral vein. Forty-eight hours later, positron emission tomography scanning was used with the tracers 15O-H2O and 18F-2-fluoro-D-glucose to analyze quantitatively CBF and CGU, respectively, in the frontoparietal and occipital regions (12 regions of interest/group). In SAH rats receiving only vehicle, CBF decreased significantly (p < 0.05, Tukey's test) and CGU tended to decrease, compared with values obtained in control (non-SAH) rats receiving vehicle. In rats that were subjected to SAH, administration of AVS significantly (p < 0.05, Tukey's test) improved CBF and CGU in both the frontoparietal and occipital regions compared with administration of vehicle alone. CONCLUSIONS: Prophylactic administration of AVS improves CBF and CGU in the rat brain subjected to SAH, and can be a good pharmacological treatment for the prevention of DINDs following SAH.

Animals↗

Detection of reperfusion injury using PET in a monkey model of cerebral ischemia.

UNLABELLED: Several studies of focal ischemia and reperfusion in animal models have proposed that reperfusion contributes to brain damage. However, the extent to which reperfusion affects the brain, especially in acute stroke patients, remains unclear. Our purpose in this study was to determine whether reperfusion injury can be detected with PET and to clarify the extent to which reperfusion contributes to brain damage. METHODS: The right middle cerebral artery (MCA) of cynomolgus monkeys was occluded for 3 h (n = 8) or permanently (n = 5) by a transorbital device. Four consecutive PET studies were performed to assess cerebral blood flow (CBF), oxygen extraction fraction (OEF), and the cerebral metabolic rate of oxygen (CMRO2). RESULTS: The extent of necrotic brain damage 8 h after MCA occlusion was significantly (P < 0.05) greater in the transient model than in the permanent model. Cortical damage was greater in the transient model. The MCA occlusion decreased CBF and CMRO2 in deep MCA territory and increased OEF in the cortex. In the permanent model, these changes continued throughout the experiment. In the transient model, the reperfusion induced postischemic hyperperfusion in the cortex, which showed necrotic damage at the end of the experiment. In this area, OEF and CMRO2 were decreased by reperfusion. CONCLUSION: The results suggest that reperfusion may strongly contribute to cortical damage. PET studies revealed that reperfusion decreased OEF and CMRO2 in the hyperperfused cortex. These changes may indicate reperfusion injury.

Animals↗

[Evaluation of population-based lung cancer screening in Niigata and analysis of interval cases based on comparison lung cancer registry with screening records].

Survival analysis has been used as one way to examine the efficacy of cancer screening. However, this type of study is susceptible to many sources of bias, especially to a length bias. In the city of Sukumo in Japan, a survival analysis considering screening history for the purpose of eliminating the length bias was conducted. The efficacy of lung cancer screening was assessed by comparing those who participated in the screening in the year preceding diagnosis, with those who did not. The 5-year survival rate was 44% in the former and 16% in the latter. We tried to evaluate population-based lung-cancer screening in Niigata using the method as that of Sukumo by comparing lung-cancer registry data with screening records, those who died of lung cancer from 1991 to 1994 in the study area and had the opportunity to be screened were categorized according to the screening history for the year preceding diagnosis. The 5-year survival rate was 41% in those who were screened and 19% in those not screened. In addition, the median survival time of the former was 37 months, significantly longer than the 12 months of the latter. Replication of study results in different populations may suggest the efficacy of lung-cancer screening on an annual basis. We also analyzed the clinical background of 47 interval cases in the search for a future direction for the improvement of the screening method.

Adult↗

Three-dimensional stereotactic surface projection analysis of macaque brain PET: development and initial applications.

UNLABELLED: To characterize better the local brain functions of conscious rhesus macaques, we developed automated image analysis techniques for monkey PET images, examined the cerebral glucose metabolism of monkeys, and compared it with that of humans. METHODS: Glucose metabolic PET images from 11 monkeys were obtained using a high-resolution animal PET scanner after intravenous administration of FDG. T1-weighted MR images were obtained from 6 of the monkeys. Referencing a bicommissural stereotactic macaque brain atlas, we created a PET brain template using coregistered MR images. Each individual PET image set was transformed to the PET template through an automated affine transformation, followed by nonlinear warping along the directions of the major neuronal fiber bundles in the brain. For minimization of residual anatomic variability, metabolic activities were extracted using 3-dimensional stereotactic surface projections. The effects of anatomic standardization were evaluated using MR images. Patterns of cerebral glucose metabolism of young versus aged monkeys were examined. The metabolic activities of aged monkeys were compared with those of elderly healthy human volunteers that had been analyzed similarly. RESULTS: Anatomic standardization reduced individuals' anatomic variability as evidenced by a reduction in the number of MR pixels with higher SDs calculated across monkeys. Coefficient-of-variation maps of conscious monkeys revealed that the greatest metabolic variances were near the central sulci and occipital cortices. Age-associated glucose metabolic reductions were most pronounced in the occipital lobe, caudate nucleus, and temporal lobe. Compared with human brains, the monkey frontal lobe and posterior cingulate gyrus had significantly less metabolic activity and the supramarginal gyrus and vermis had significantly more metabolic activity. CONCLUSION: The proposed method permits pixel-by-pixel characterization of the metabolic activities of rhesus macaque brains in the stereotactic coordinate system. Greater metabolic variances in the central sulcus region and occipital lobe suggest potential difficulties in controlling sensory input and motor output or planning in conscious monkey experiments. The analyses revealed age-related metabolic reductions in monkeys and marked differences in metabolic patterns between aged monkey brains and aged human brains. The proposed brain-mapping technique enables reproducible and observer-independent analyses and will serve as an important investigative tool for primate brain imaging research.

Aging↗

Isoflurane anesthesia enhances the inhibitory effects of cocaine and GBR12909 on dopamine transporter: PET studies in combination with microdialysis in the monkey brain.

The effects of the dopamine transporter (DAT) inhibitors cocaine and GBR12909 on DAT and dopamine D(2) receptors were evaluated in the brains under awake and isoflurane-anesthetized monkeys using high-resolution positron emission tomography (PET) in combination with microdialysis. The striatal DAT availability and dopamine D(2) receptor binding were assayed with [11C]beta-CFT (WIN35,428) and [11C]raclopride, respectively. Cocaine or GBR12909 at a dose of 2 mg/kg was administered intravenously 30 min prior to the injection of labeled compounds. In the awake state, the in vivo binding of [11C]beta-CFT to DAT was significantly decreased by administration of cocaine or GBR12909 at a dose of 2 mg/kg. In contrast, [11C]raclopride binding to dopamine D(2) receptors was decreased only by GBR12909. Under isoflurane anesthesia, dopamine concentration in the striatal extracellular fluid (ECF), as measured by microdialysis, was markedly increased by cocaine or GBR12909 compared to the awake state. Isoflurane anesthesia more markedly enhanced the binding of [11C]beta-CFT in the saline-injected animals, and the degrees of reduction by cocaine and GBR12909 were more marked than those observed in the awake state. Under isoflurane anesthesia, the binding of [11C]raclopride was reduced not only by GBR12909 but also by cocaine which did not affect the binding in the awake state. Taken together, these observations indicated that isoflurane anesthesia enhanced not only the direct inhibitory effects of cocaine and GBR12909 on DAT, but also their indirect effects on dopamine D(2) receptors.

Anesthesia, Inhalation↗

Is synaptic dopamine concentration the exclusive factor which alters the in vivo binding of [11C]raclopride?: PET studies combined with microdialysis in conscious monkeys.

The effects of dopamine release manipulated by drugs on the in vivo binding of [11C]raclopride in the striatum were evaluated in conscious monkeys combined with microdialysis. The in vivo binding of [11C]raclopride was evaluated by high resolution positron emission tomography (PET), and the dopamine concentrations in the striatal extracellular fluid (ECF) were measured by microdialysis in the same animals. The systemic administration of the direct dopamine enhancers, GBR12909 (a dopamine transporter (DAT) blocker, at 0.5, 2 and 5 mg/kg) or methamphetamine (a dopamine releaser, at 0.1, 0.3 and 1 mg/kg) dose-dependently increased the dopamine concentration in the striatal ECF, and decreased in vivo [11C]raclopride binding in the striatum. The administration of the indirect dopamine modulators benztropine (a muscarinic cholinergic antagonist, at 0.1, 0.3 and 1 mg/kg) or ketanserine (a 5-HT2 antagonist, at 0.3, 1 and 3 mg/kg) also increased dopamine level in the striatal ECF, and decreased [11C]raclopride binding in a dose-dependent manner. However, the plots of percentage change in dopamine concentration in striatal EFC against that in [11C] raclopride binding indicated different relationships between the effects of direct dopamine enhancers (GBR12909 and methamphetamine) and indirect dopamine modulators (benztropine and ketanserine). These results suggested that the alternation of [11C]raclopride binding in vivo as measured by PET was differently affected by different neuronal manipulations, and not simply by the synaptic concentration of dopamine.

Animals↗

The role of Pseudomonas aeruginosa elastase as a potent inflammatory factor in a rat air pouch inflammation model.

Pseudomonas aeruginosa, an opportunistic pathogen, can cause life threatening infections in patients compromised by underlying respiratory disease like bronchiectasis, cystic fibrosis and diffuse panbronchiolitis. Most strains of P. aeruginosa produce some kind of protease with broad substrate specificities during the infectious state in the host. P. aeruginosa elastase, one of the strongest exotoxins, has a tissue-damaging proteolytic activity and is capable of degrading such plasma proteins as immunoglobulins, complement factor and cytokines. The present study focused on the effect of P. aeruginosa elastase and was designed to evaluate the neutrophil accumulation at the inflammation site mediated by P. aeruginosa elastase in the inflammatory response in the host. An air pouch model in rats, considered as a useful model of inflammation, was used to analyze the number of leukocytes, the volume of exudate and the concentration of interleukin-8 after the injection of P. aeruginosa elastase into the pouch cavity. The number of neutrophils and the volume of exudate in the pouch cavity increased significantly at 4 h, peaked at 8 h in a dose-dependent manner and then decreased at 24 h. The concentration of interleukin-8 in pouch fluid peaked 4 h earlier than the peak of the neutrophil number. The enzymatic activity of P. aeruginosa elastase seemed to reinforce the inflammation process. The influence of lipopolysaccharide contamination was negligible. Although these observations were made in the subcutaneous cavity, they indicate that P. aeruginosa elastase plays a role as an immunoprovocative factor in the inflammatory response in cases of infection with P. aeruginosa.

Air↗

The effect of sequential lesioning in the basal forebrain on cerebral cortical glucose metabolism in rats. An animal positron emission tomography study.

We studied the effect of the cortical projection from the basal forebrain on the cerebral cortical metabolism using positron emission tomography (PET) with [(18)F] fluorodeoxyglucose. Unilateral damage of the nucleus basalis magnocellularis (NBM) did not cause a permanent reduction of cortical metabolism: recovery was observed 4 weeks after the operation. Destruction of the contralateral side after recovery from unilateral damage produced persistent bilateral suppression of glucose metabolism, with partial recovery. We speculate that recovery from the unilateral NBM lesions is partly ascribable to the cholinergic projection from the contralateral NBM, and partly due to non-cholinergic systems, and conclude that bilateral damage might be responsible for persistent cortical glucose metabolism suppression.

Animals↗

Cerebral glucose metabolism in unilateral entorhinal cortex-lesioned rats: an animal PET study.

To evaluate the effect of entorhinal cortical lesion on cerebral cortical function, we studied cerebral glucose utilization (CMRGlc) using a high resolution PET scanner after quinolinic acid lesion of the unilateral entorhinal cortex in rats. [18F]Fluorodeoxyglucose PET was performed at 4 days and 4 weeks after surgery, and CMRGlc in the bilateral frontal, parietal and temporal regions were analyzed. At 4 days, the entorhinal lesion induced a 12-15% decrease in CMRGlc of frontal, parietal and temporal regions ipsilateral to the lesion. The hypometabolism continued at 4 weeks in the temporal region. These findings suggest that entorhinal lesion induces cerebral cortical hypometabolism, which implies a pathogenetic role of entorhinal area on the cortical hypometabolism in Alzheimer's disease.

Analysis of Variance↗

FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, restores the regional cerebral blood flow response abolished by scopolamine but not by HA-966: a positron emission tomography study with unanesthetized rhesus monkeys.

The interactions of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, with cholinergic and glutamatergic neuronal systems were evaluated with respect to its effects on the regional cerebral blood flow (rCBF) response to vibrotactile stimulation in unanesthetized rhesus monkeys with [15O]H2O and high resolution positron emission tomography (PET). Under a saline condition, the vibrotactile stimulation given on the right forepaw induced a significant increase in the rCBF response in the contralateral somatosensory cortex of the monkey brain. Systemic administration of scopolamine (50 microg/kg, i.v.), a muscarinic cholinergic receptor antagonist, completely abolished the rCBF response to the stimulation, and the abolishment lasted, at least, up to 4 h after scopolamine injection. The scopolamine-induced abolishment of rCBF response was restored by the administration of FK960 at relatively wide dosing range from 1 to 1000 microg/kg (i.v. ), and the recovery by FK960 on the rCBF response lasted for 1 h following the administration of FK960 at doses of 100 and 1000 microg/kg. On the other hand, the rCBF response abolished by 1000 microg/kg of (+)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), an antagonist of the glycine modulatory site on the N-methyl-d-aspartate (NMDA) receptors, was not restored by FK960 (1000 microg/kg, i.v.). These findings suggest that FK960 reverses the abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission but not via the glutamatergic one.

Animals↗

Transfer of 137Cs and stable Cs from soil to potato in agricultural fields.

The concentrations of 137Cs, stable Cs and K were measured in soils and potatoes collected from 26 agricultural fields in Aomori, Japan and soil-to-potato transfer factors of 137Cs and stable Cs were determined. The concentrations of 137Cs derived from fallout deposition and stable Cs in soils were 1-37 Bq kg-1 and 1-11 mg kg-1, respectively. The isotopes, 137Cs and stable Cs, were homogeneously mixed in the rooting zone in the upper 20 cm of soil in agricultural fields. The concentrations of 137Cs and stable Cs in potatoes were 50-2000 mBq kg-1 dry wt. and 0.004-0.13 mg kg-1 dry wt., respectively. The soil-to-potato transfer factor of 137Cs was in the range of 0.0037-0.16, which was higher than that of stable Cs of 0.00052-0.080. The transfer factors of 137Cs and stable Cs were correlated and the geometric mean of 137Cs was 0.030, which was four times higher than that of stable Cs at 0.0075. This implied that artificially added 137Cs is more mobile and more easily absorbed by plants than stable Cs in the soil. The concentration of K in potatoes showed a relatively constant value, independent of that in the soil. The transfer factors of both 137Cs and stable Cs decreased with increasing K concentration in the soil, which was mainly supplied as fertilizers to the fields. This suggests that the transfer of both 137Cs and stable Cs from soil to potato was affected by the presence of K in the soil. However, the transfer factors of 137Cs and stable Cs were independent of the amount of organic materials in soils.

Cesium↗

Delivery of radioligands for positron emission tomography (PET) in the central nervous system.

Positron emission tomography (PET) is an imaging technique to monitor the delivery of tracers labeled with positron emitters ((11)C, (13)N, (15)O and (18)F). A wide variety of probes have been labeled to measure biochemical and physiological parameters in the central nervous system (CNS), such as glucose and oxygen metabolism, protein synthesis, blood flow, and neurotransmitter receptor functions. The delivery of labeled compounds to the target tissue, which directly reflect the distribution and kinetics patterns, especially to the neurotransmitter receptors is modulated by several factors, such as regional cerebral blood flow (rCBF), peripheral metabolism, and neurotransmitter concentration in the synaptic cleft. These factors provide misunderstanding of the apparent results, which do not reflect the true state of the CNS. The present paper will summarize several factors that affect the delivery of labeled compounds related to the neurotransmitter receptors in the CNS.

Journal Article↗

The effect of aniracetam on cerebral glucose metabolism in rats after lesioning of the basal forebrain measured by PET.

To evaluate the effect of aniracetam, a potent modulator of the glutamatergic and cholinergic systems, on the altered cerebral glucose metabolism after lesioning of the basal forebrain, we measured the cerebral metabolic rate of glucose (CMRGlc) with positron emission tomography and the choline acetyltransferase (ChAT) activity in the frontal cortex of the lesioned rats after treating them with aniracetam. Continuous administration of aniracetam for 7 days after the surgery prevented CMRGlc reduction in the frontal cortex ipsilateral to the lesion while the lesioned rats without aniracetam showed significant CMRGlc reduction in the frontal cortex. The level of CMRGlc in the lesion-side basal forebrain was lower in all rats regardless of the aniracetam treatment. Biochemical studies showed that aniracetam did not alter the reduction in the frontal ChAT activity. These results showed that aniracetam prevents glucose metabolic reduction in the cholinergically denervated frontal cortex with little effect on the cortical cholinergic system. The present study suggested that a neurotransmitter system other than the cholinergic system, e.g. the glutamatergic system, plays a central role in the cortical metabolic recovery after lesioning of the basal forebrain.

Animals↗

Activation of the insular and opercular regions of the monkey by drinking as revealed by positron emission tomography.

We measured the regional cerebral blood flow (rCBF) of the monkey using positron emission tomography (PET) in the following conditions: self-initiated (SELF), visually-initiated (VISUAL), and color-discriminating go/no-go (GONOGO) hand movement tasks with reward of water, free reward condition (REWARD), and resting states (REST). The insulae, frontal opercula, and mouth sensorimotor area were activated in any of SELF, VISUAL, GONOGO, and REWARD, when compared with REST. These findings suggest that the insular and opercular regions play an important role in the neural processes involved in drinking.

Animals↗