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Biomedical subjects

H Tsukada

Publications and source records attributed to H Tsukada.

At least 127 records · Page 7Linked to original sources
PubMed1997

Mapping of cortical areas involved in color vision in non-human primates.

Positron emission tomography (PET) was used to measure changes in the regional cerebral blood flow (rCBF) of rhesus monkeys performing visual discrimination tasks. In comparison with both position and brightness discrimination tasks, the color discrimination task activated the posterior inferior temporal cortex and a ventromedial occipital region, which is located along the anterior one-third of the calcarine sulcus. In contrast, the position task activated the middle temporal area and intraparietal cortex as compared with the color task. These results confirm the segregation of visual pathways and delineate the visual areas involved in color vision. This approach might bridge the gap between invasive studies in animals and functional imaging studies in humans.

Animals↗
PubMed1997

Activation of the prefrontal, occipital and parietal cortices during go/no-go discrimination tasks in the monkey as revealed by positron emission tomography.

The regions of the monkey brain involved in cognito-behavioral tasks were mapped using the H2(15)O positron emission tomography (PET) activation technique. Monkeys performed hand movements in an asymmetrically rewarded go/no-go reaction-time task with discrimination between green (go) and red (no-go) light signals. Regional cerebral blood flow (rCBF) was measured during the go/no-go task and a control task in which only go signals were presented. In the go/no-go task, when compared with the control, a significant increase in rCBF was noted in the following regions: (1) the principal sulci; (2) the anterodorsal frontal pole; (3) the anterior part of the inferior occipital sulcus which appeared to be the V4; and (4) the parieto-occipital region. The increase in the principal sulci may be related to the no-go decision and motor suppression in the area, as interpreted in our previous electrophysiological studies. The present results appear to support electrophysiological observations on visual perception and motor suppression and reflect a mode of their functional integration.

Animals↗
PubMed1997

Regulation of cerebral blood flow response to somatosensory stimulation through the cholinergic system: a positron emission tomography study in unanesthetized monkeys.

The effects of scopolamine, a muscarinic cholinergic receptor antagonist and physostigmine, a cholinesterase inhibitor, on the regional cerebral blood flow (rCBF) response to vibrotactile stimulation of the forepaw were studied in the brain of unanesthetized monkeys using 15O-labeled water and high resolution positron emission tomography. Before scopolamine administration, vibrotactile stimulation produced a significant increase in the rCBF response in the contralateral somatosensory cortex of the monkey brain. Intravenous administration of scopolamine at doses ranging from 1 to 500 microg/kg resulted in a dose-dependent reduction of the rCBF response. The rCBF response abolished by scopolamine (50 microg/kg) was recovered by administration of physostigmine (10 microg/kg). On the other hand, the regional cerebral metabolic rate of glucose (rCMRglc) response, measured with [18F]-2-fluoro-2-deoxy-D-glucose, to the same stimulation was unchanged by administration of either scopolamine and/or physostigmine. These results suggested that cholinergic mechanisms might be involved in regulation of the coupling between neuronal activity and rCBF response, not between the activity and rCMRglc response.

Animals↗
PubMed1997

Dose- and route-dependent alterations in metabolism and toxicity of chemical compounds in ethanol-treated rats: difference between highly (chloroform) and poorly (carbon tetrachloride) metabolized hepatotoxic compounds.

The dose and route dependency of the metabolism and the toxicity of chloroform (CHCl3) and carbon tetrachloride (CCl4) was investigated in ethanol-treated rats. Rats that had been kept on either an ethanol (containing ethanol at 2 g/rat/day) or a control (containing no ethanol) liquid diet for 3 weeks were challenged with CHCl3 or CCl4 by inhalation (0, 50, or 500 ppm x 6 hr), or by p.o. or i.p. administration (0, 0.105, or 1.675 mmol/kg). Ethanol consumption, which increased the in vitro metabolism of both compounds six- to sevenfold, affected the metabolism and toxicity of CCl4 differently from those of CHCl3. Ethanol increased the metabolism and toxicity of CHCl3 at 500 ppm only, whereas it increased the metabolism and toxicity of CCl4 at either 50 or 500 ppm. In addition, the effect of ethanol consumption differed between CHCl3 and CCl4 depending on the route of administration (p.o. or i.p.) and the dose (0.105 or 1.675 mmol/kg). For the p.o. route, ethanol increased the metabolism and toxicity of both compounds at either dose. For the i.p. route, however, ethanol increased the metabolism and toxicity of the high dose of CHCl3 only, but of both CCl4 doses. The dose- and route-dependent differences in the effect of enzyme induction on the metabolism and toxicity between CHCl3 and CCl4 can be explained by a supposition that the hepatic blood flow rate-limits the metabolism of a low dose of CHCl3 (perfusion-limited metabolism), whereas the metabolic capacity of the liver limits the metabolism of CCl4 (capacity-limited metabolism) irrespective of dose.

Administration, Inhalation↗
PubMed1997

Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes.

The relationship was investigated between biochemical and morphological changes in chloroform (CHCl3)- and carbon tetrachloride (CCl4)-induced liver damage. The time courses of hepatic microsomal cytochrome P450 (CYP) content, hepatic microsomal CYP2E1 activity, hepatic reduced glutathione (GSH) content, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were examined in relation to the liver morphology in rats orally treated with CHCl3 or CCl4 (3.35 mmol/kg). The CYP content and the activity of CYP2E1 markedly decreased in the CCl4-treated rats 3 h after treatment compared to much lower decreases in the CHCl3-treated rats. The hepatic GSH content was decreased to a similar extent in both groups of rats at 3 h after treatment; in the CCl4-treated rats, the GSH content continued to decrease, reaching a minimum at 24 h and without attaining the normal level at 72 h after treatment. By contrast, hepatic GSH content in the CHCl3-treated rats began to increase from 6 h, attaining complete recovery 48 h after treatment. Plasma ALT and AST activities were significantly elevated by CCl4 as early as 3 h after treatment, while the activities in the CHCl3-treated rats did not increase until 6 h after treatment. In both groups of rats, ALT and AST activities reached a maximum at 24 h, and gradually decreased, remaining at abnormal levels at 72 h. Hepatic cells in the CCl4-treated rats were found to be necrotic as early as 3 h post-treatment, whereas few or no morphological changes appeared in the liver of CHCl3-treated rats. The extent of necrosis was at a maximum 24 h after treatment in both CHCl3- and CCl4-treated rats. In addition, some necrotic cells remained in the liver of CCl4-treated rats 72 h after treatment, while the necrosis in the CHCl3-treated rats was almost negligible. The present results indicate that almost the same time-courses of biochemical and morphological changes were followed in rats of both the CHCl3- and CCl4-treated groups.

Administration, Oral↗
PubMed1997

A novel near infra-red spectrophotometry system using microprobes: its evaluation and application for monitoring neuronal activity in the visual cortex.

A novel near-infrared (NIR) spectrophotometry system with microprobes of optical transmitter and receivers (550 and 410 microm in diameter, respectively) has been developed. A three-dimensional profile of the signal source estimated in in vitro experiments showed two spindle-shaped regions around the respective probes, suggesting that the signal detected by the present system comes from a relatively restricted region around each probe. Next, we examined how the concentration of oxygen in inspired gas affected the NIR signals in the rat cerebral cortex in vivo. Calculated concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) in the rat cortex changed in mirror-image fashion in response to the change in the O2 concentration in the inspired gas. Finally, NIR responses to visual stimulation were recorded from the striate cortex of conscious adult cats that had been monocularly deprived since the peak of the sensitive period. Corresponding to the results of previous electrophysiological studies, stimulation of the normal eye induced significant NIR signals, whereas that of the deprived eye evoked no response. These results indicate that this new NIR system can be applied to study changes in oxygen metabolism in relatively restricted regions following neuronal activation in the brain.

Animals↗
PubMed1997

Effects of a thromboxane A2 receptor antagonist in an animal model of inflammatory bowel disease.

BACKGROUND/AIMS: We evaluated the effects of an antagonist of the thromboxane A2 receptor (ONO-NT-126) in an animal model of inflammatory bowel disease (IBD). METHODS: Colitis was induced by intracolonic instillation of trinitrobenzenesulfonic acid/ethanol in male Wistar rats. ONO-NT-126 or vehicle alone was administered intraluminally via anus once a day. The rats were killed after 7 days for assessment of colonic damage by the colonic damage score. RESULTS AND CONCLUSION: ONO-NT-126 markedly reduced the colonic damage. Our findings suggest that the thromboxane-thromboxane receptor system plays an important role in this model of IBD and that antagonism of the thromboxane A2 receptor may prove useful for the treatment of IBD.

Animals↗
PubMed1997

Application of long-circulating liposomes to cancer photodynamic therapy.

Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.

Animals↗
PubMed1997

[The effect of cerebral perfusion pressure on cerebral blood flow in the rhesus monkey during sevoflurane anesthesia].

The effect of cerebral perfusion pressure on cerebral blood flow (CBF) was studied under the normocapnic condition in the rhesus monkey under sevoflurane anesthesia. CBF was measured by means of positron emission tomography technique. After the measurement of CBF at 0.5% sevoflurane as control, the measurement was repeated at 2.0% sevoflurane (1 MAC), when blood pressure was kept at a half of the control value. The measurement was also repeated at the same sevoflurane concentration, when the mean blood pressure was restored with the infusion of angiotensin II. Average CBF as well as regional CBFs were compared between two different mean blood pressures at 2.0% sevoflurane. Average CBF increased significantly (+35%), when the mean arterial pressure was increased by the angiotensin II infusion. All the regional CBFs except at frontal cortex increased significantly (+ about 30%) in response to the increase in the mean arterial pressure. The increase in occipital CBF was greatest (+52%). We conclude that CBF during sevoflurane anesthesia up to 2.0% might become dependent on the cerebral perfusion pressure, indicating the compromised autoregulation of CBF in the rhesus monkey.

Anesthesia, Inhalation↗
PubMed1997

[The effect of sevoflurane on regional cerebral metabolism and cerebral blood flow in rhesus monkeys].

The effects of sevoflurane on cerebral metabolism and hemodynamics were studied in rhesus monkeys. Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMR O2) as well as their regional changes were measured by means of positron emission tomography technique. After the measurement of regional CBFs and CMR O2s at 1.5% sevoflurane as control, the measurement was repeated at 3.0% sevoflurane and at the same sevoflurane concentration with the infusion of angiotensin II to restore mean arterial pressure. Regional CBFs and CMR O2s were compared among three different conditions. At 3.0% sevoflurane, regional CBFs increased significantly in response to the increase in the mean arterial pressure, suggesting the inhibition of autoregulation of CBF. However, regional CBF/CMR O2 ratio was not significantly different among the cerebral regions with each condition. It could be concluded that CBF during sevoflurane anesthesia up to 3.0% might become dependent on the cerebral perfusion pressure and the changes in regional CBFs varied among the regions. On the other hand, the ratio of oxygen consumption and delivery was well maintained throughout the brain regions.

Anesthesia, Inhalation↗
PubMed1997

Functional activation of cerebral blood flow abolished by scopolamine is reversed by cognitive enhancers associated with cholinesterase inhibition: a positron emission tomography study in unanesthetized monkeys.

The effects of somatosensory stimulation on the regional cerebral blood flow (rCBF) response were studied in unanesthetized monkeys before and after treatment with scopolamine and three cognitive enhancers (physostigmine, E2020 and tacrine) that inhibit cholinesterase, using 15O-labeled water and high-resolution positron emission tomography. Under control conditions, somatosensory stimulation induced a significant increase in the rCBF response in the contralateral somatosensory cortex of monkey brain. Intravenous administration of scopolamine (50 microg/kg) resulted in abolishment of the rCBF response to stimulation. The rCBF response abolished by pretreatment with scopolamine was recovered by administration of physostigmine (1 or 10 microg/kg), E2020 (10 or 100 microg/kg) or tacrine (100 or 1000 microg/kg), in a dose-dependent manner. The effect of E2020 (100 microg/kg) on the rCBF response lasted for >4 hr, whereas the effects of physostigmine and tacrine were of shorter duration. These findings suggest that these compounds reversed the scopolamine-abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission, which was mainly induced by cholinesterase inhibition.

Animals↗
PubMed1997

[CT-guided lung needle biopsy using a new supporting implement].

We contrived a new supporting implement to increase the hit rate of CT-guided needle biopsy (CTNB) for localized pulmonary lesions. Using this implement, twenty-two CTNB examinations for localized pulmonary lesions were performed. In 21 out of the 22 examinations (95%), the lesions were hit, and specimens appropriate for cytological or histological diagnosis were obtained. The course of needle insertion, which was difficult to define in the past, has become to be easier and more precise with this method. Using this new implement, CTNB is now applicable to smaller and deeper lesions.

Adult↗
PubMed1996

A subclass of GABAA/benzodiazepine receptor exclusively localized in the limbic system.

An in vivo saturation study using 11C-labelled Ro15-4513 with high specific radioactivity (> 70 GBq mumol-1) revealed the presence of very high-affinity and high-affinity binding sites (Kd values in the amygdala approximately 0.4 and 18.7 nM, respectively) in the gamma-aminobutyric acid type A/benzodiazepine (GABAA/BZ) receptor in the living monkey brain. Subtraction of an image obtained using [11C]Ro15-4513 with low specific radioactivity from an image obtained by that with high specific radioactivity, both of which were scanned with a high spatial resolution positron emission tomography camera, demonstrated that the very high-affinity sites are exclusively localized in the limbic system, such as in the amygdala, hippocampus, anterior cingulate, septum, nucleus accumbens and insular cortex. The localization of the very high-affinity binding sites, which may be derived from a subclass of central GABAA/BZ receptors, might account for the anxiolytic effect of BZ analogues.

Affinity Labels↗
PubMed1996

Effects of binge pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain: an in vivo study using positron emission tomography.

The aim of the present study was to determine the effect of "binge" pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain. Male Sprague Dawley rats were injected three times at 1 hr intervals with saline or cocaine (15 mg/kg) each day for 2, 7, or 14 d. The in vivo binding of [11C]SCH23390 (dopamine D1 receptor antagonist) and [11C]N-methylspiperone (NMSP; dopamine D2 receptor antagonist) in the striatal region was measured by a high-resolution positron emission tomography at 1 and 3.5 hr, respectively, after the last cocaine or saline injection. Acute (2 d) binge cocaine administration did not change the in vivo binding potential of [11C]SCH23390 or the binding of [11C]NMSP in the striatum. After 7 d of binge cocaine administration, a significant decrease in the binding potential of [11C]SCH23390 was observed, whereas no change in the binding of [11C]NMSP was found. After 14 d of binge cocaine administration, the in vivo binding was significantly reduced for both [11C]SCH23390 and [11C]NMSP. Separate saturation experiments indicated that the observed alterations of in vivo binding were attributable mainly to apparent alterations in the affinity and not the number of binding sites. These results suggest that both dopamine D1 and D2 receptors may have altered physiologically available binding sites after binge pattern cocaine administration.

Animals↗
PubMed1996

Adoptive immunotherapy with tumor-specific T lymphocytes generated from cytokine gene-modified tumor-primed lymph node cells.

Adoptive immunotherapy with immune T cells mediates regression of established tumors in animal models. We previously demonstrated that precursor lymphocytes of sensitized T cells can develop into mature effector cells after in vitro activation with anti-CD3 mAb and IL-2. We demonstrate here that tumor cells genetically modified to secrete IL-2 can enhance the precursor response in the tumor-bearing host and subsequently augment the antitumor efficacy of adoptive immunotherapy. MCA205 and MCA203, weakly immunogenic fibrosarcomas, were transfected in vitro with cDNA encoding for IL-2, IL-4, or IL-6. Lymph nodes (LN) draining these cytokine-producing tumors for 7 days were harvested, activated in vitro with anti-CD3/IL-2, and adoptively transferred into mice bearing established parental MCA205 pulmonary metastases. The effector cells generated from LN draining the IL-2 producing tumor exhibited enhanced antitumor activity compared with cells from LN draining parental, IL-4-producing, or IL-6-producing tumor. Phenotype analysis of cells from LN draining the IL-2-producing tumor revealed selective expansion of V beta 8+ cells. Depletion of V beta 8+ effector cells abrogated the antitumor efficacy indicating that V beta 8+ cells constituted the majority of antitumor reactivity and that secretion of IL-2 from tumor cells promoted the priming of V beta 8+ precursor cells, which can develop into mature effector cells. These results have important clinical implications that the method presented here could be applicable to the treatment of human cancer as more effective immunotherapy.

Animals↗
PubMed1996

Effect of serum protein binding on real-time trafficking of liposomes with different charges analyzed by positron emission tomography.

Liposomes have been used as carriers of various materials and as tools for gene transfer: for the latter purpose, positively charged liposomes are usually used. To evaluate the stability in the presence of serum and the in vivo behavior of such liposomes as well as those aspects of neutral and negatively charged liposomes, we investigated liposomal agglutinability in the presence of serum, serum protein binding to these liposomes, and real-time liposomal trafficking by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol without or with charged lipid were prepared in the presence of mannitol, and the turbidity change in the presence of serum was determined. Turbidity increase was not observed for so-called long-circulating liposomes, i.e., liposomes modified with glucuronic acid or with poly(ethylene glycol), or for negatively charged liposomes containing dicetyl phosphate (DCP), phosphatidylglycerol, or phosphatidylserine. On the contrary, a significant turbidity increase was observed when positively charged liposomes modified with stearylamine, stearyltrimethylammonium chloride or 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl bromide (DMRIE), which is known as a component of liposomes for gene transfer, were used. These liposomes were found to have bound a high amount of serum proteins after separation of unbound serum proteins by use of a spin column. The liposomal trafficking in vivo was determined for three kinds of liposomes, i.e., liposomes with DMRIE, those with DCP, and those without charged lipids. These liposomes were prepared in the presence of 2-[18F]fluoro-2-deoxy-D-glucose ([2-18F]FDG), and the [2-18F]FDG-labeled liposomes were administered to mice to perform PET scans. Positively charged liposomes containing DMRIE showed high accumulation in the liver compared with neutral and negatively charged liposomes. Since DMRIE-liposomes tended to aggregate in the presence of serum, and to be associated with serum protein, these characteristics may lead to the high uptake of DMRIE-liposomes by the liver.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin and infusion of L-tyrosine on the in vivo L-[beta-11C] DOPA disposition in the monkey brain.

The effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) and L-tyrosine infusion on [11C]dopamine synthesis was analyzed in the striatum of Rhesus using positron emission tomography (PET). The rate for decarboxylation from L-[beta-11C]DOPA to [11C]dopamine was calculated using a graphical method with cerebellum as a reference region. Although the peripheral administration of 6R-BH4 at low dose (2 mg/kg) did not provide a significant increase in the rate of dopamine biosynthesis, a high dose of 6R-BH4 (20 mg/kg) induced an elevation of the rate. This 6R-BH4-induced elevation of the dopamine synthesis rate was further dose-dependently enhanced by the continuous infusion of L-tyrosine (0.2 and 1.0 mumol/min/kg). L-Tyrosine infusion with a rate of 1.0 mumol/min/kg caused an enhancement of the rate even during low dose administration of 6R-BH4 (2 mg/kg). L-Tyrosine infusion alone did not induce any elevation of the dopamine biosynthesis rate. The analysis of plasma indicated that the metabolic ratios of L-[beta-11C]DOPA to each metabolite were not affected by 6R-BH4 and/or L-tyrosine infusion. The results suggest that the low dose loading of tyrosine facilitates the activity of 6R-BH4 on the presynaptic dopamine biosynthesis, and also that the combined effects can be monitored by PET using L-[beta-11C]DOPA as a biochemical probe.

Animals↗