Biomedical subjects

H Tsukada

Publications and source records attributed to H Tsukada.

At least 55 records · Page 3Linked to original sources

PubMed2000

Changes in local cerebral blood flow in photochemically induced thrombotic occlusion model in rats.

We demonstrated earlier that in a photochemically induced thrombotic occlusion model, a reperfusion-like phenomenon may be involved in the progress of brain damage. Therefore, we now investigated changes in local cerebral blood flow in a photochemical model compared with changes in a thermocoagulated occlusion model, using autoradiography. At 5 min, and 3, 6 and 24 h after middle cerebral artery occlusion, local cerebral blood flow was measured by intravenous injection of 4-iodo[N-methyl-14C]antipyrine (20 mu Ci). In the ischemic core zone, the reduction in blood flow was similar in the two models. However, blood flow in the ischemic border zone in the photochemical model decreased transiently in the third hour after ischemia and then increased again, while the blood flow in a thermocoagulated model continued to decrease. Time courses of brain damage formation in both models were no different up to 24 h. These findings suggest that the transient reduction in cerebral blood flow in the third hour following ischemia may contribute to a reperfusion-like phenomenon in a photochemical model.

Animals↗

PubMed2000

Treatment of roentgenographically occult endobronchial carcinoma with external beam radiotherapy and intraluminal low-dose-rate brachytherapy: second report.

PURPOSE: To evaluate the efficacy and toxicity of treatment with external beam radiotherapy and intraluminal low-dose-rate brachytherapy for roentgenographically occult endobronchial carcinoma (ROEC). METHOD AND MATERIALS: A total of 79 lesions (71 cases) of ROEC were treated with external beam radiotherapy and intraluminal low-dose-rate brachytherapy from July 1991 to December 1998. Of these lesions, 68 (64 cases) were treated with our standard dose (external beam radiotherapy of 40 Gy and intraluminal low-dose-rate brachytherapy of 25 Gy) and are the subject of this report. All 64 patients were males, and their ages ranged from 55 to 80 (median, 68) years. The histologic diagnosis was squamous cell carcinoma in all patients. RESULTS: In all cases, the scheduled treatment was carried out within 2 months. Follow-up period ranged from 4 to 91 (median, 44) months from the beginning of this treatment. Acute toxicity was tolerable. Grade 2 radiation pneumonitis was observed in 4 cases, and there was no case of greater than Grade 2 radiation fibrosis. Nineteen cases of bronchial stenosis and 23 cases of bronchial obstruction were observed on follow-up bronchoscopy. However, no Grade 2 or greater deterioration of respiratory function due to radiotherapy, prolonged symptoms, or fatal toxicity was observed. Nine patients suffered recurrence, 5 of whom were rescued by surgery and external beam radiotherapy, and 4 of whom died of disease. The 5-year cause-specific survival, overall-survival, and disease-free rate were 96.1%, 72.3%, and 87.3%, respectively. CONCLUSION: Combined treatment with external beam radiotherapy and intraluminal low-dose-rate brachytherapy is effective and results in acceptable complications for ROEC.

Aged↗

PubMed2000

Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys.

The regional cerebral blood flow (rCBF) response to vibrotactile stimulation was compared in conscious young (5.9+/-1.8 years old) and aged (18.0+/-3.3 years old) monkeys using [15O]H(2)O and high-resolution positron emission tomography (PET). In addition, the effects of docosahexaenoic acid (DAH), an n-3 polyunsaturated fatty acid (PUFA), on the rCBF response to stimulation were evaluated in aged monkeys. Soybean milk (SBM) or DHA-containing SBM (DHA/SBM) was supplied to aged monkeys for 1 and 4 weeks. Under control conditions, vibrotactile stimulation elicited an increase in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in the rCBF response was significantly lower in aged monkeys (116% of corresponding 'rest' condition) than that in young animals (141%). The regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, an index of neuronal activation, was not significantly different between young and aged monkeys as measured by [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Supply of DHA/SBM at a dose of 150 mg/kg/day as DHA for 1 week resulted in a significant increase in rCBF response to stimulation (127%) in aged monkeys, and 4-week supply of DHA induced further facilitation of the rCBF response (133%). In contrast, the reduced rCBF response in the aged monkeys was not affected by SBM alone for either 1 or 4 weeks. The neuronal activation itself elicited by the stimulation, as measured by [18F]FDG, was not affected by SBM or DHA/SBM. These results suggested the involvement of DHA in the coupling mechanism between the neuronal activation and rCBF response, possibly by modulation of cholinergic neuronal transmission.

Aging↗

PubMed2000

Dose-response and duration effects of acute administrations of cocaine and GBR12909 on dopamine synthesis and transporter in the conscious monkey brain: PET studies combined with microdialysis.

The dose-response and duration effects of acute administration of the dopamine transporter (DAT) blocker cocaine and GBR12909 on dopamine synthesis and transporter availability were evaluated in the brains of conscious monkeys using high-resolution positron emission tomography (PET) in combination with microdialysis. Rate of dopamine synthesis and DAT availability were evaluated using L-[beta-11C]DOPA and [11C]beta-CFT (WIN35,428), respectively. Administration of cocaine (0.5, 2 and 5 mg/kg) resulted in dose-dependent elevation of dopamine level in the striatal extracellular fluid (ECF) at 0.5 h after injection, and returned to the baseline level within 1.5 h post-injection. At 0.5 post-injection, cocaine reduced dopamine synthesis rate and DAT availability in a dose-dependent manner. The reduction of DAT availability by cocaine (2 mg/kg) returned to baseline level at 3 h post-injection and thereafter. Interestingly, dopamine synthesis rate was significantly higher at 3 h than baseline level and returned to baseline level 5.5 h post-injection. When GBR12909 (0.5, 2 and 5 mg/kg) was administered 0.5 h before tracer injection, dopamine synthesis rate and DAT availability were significantly decreased in a dose-dependent manner. These reductions induced by GBR12909 (2 mg/kg) lasted at least until 5.5 h post-injection. GBR12909 induced dose-dependent elevation of dopamine level in ECF, and the elevation lasted up to 7 h. The present results indicated that cocaine and GBR12909 affect dopamine synthesis rate and DAT availability in the striatum with difference time courses as measured by PET in the conscious monkey brains.

Animals↗

PubMed2000

Decline of the monkey's limbic and prefrontal activity during task repetition.

In order to investigate the neural mechanism underlying the motivation, we measured the regional cerebral blood flow (rCBF) by positron emission tomography in a monkey that was repeatedly engaged in cognito-behavioural tasks. The rCBF of the anterior cingulate area, medial parts of prefrontal area, and hippocampal region decreased significantly with the succession of tasks within a day. The activity was restored abruptly when the reward was then increased, but decreased again on further repetition of the tasks. These findings suggest that the limbic and prefrontal areas are the regions involved in motivational function in the brain.

Animals↗

PubMed2000

Age-related impairment of coupling mechanism between neuronal activation and functional cerebral blood flow response was restored by cholinesterase inhibition: PET study with microdialysis in the awake monkey brain.

The effects of three cholinesterase inhibitors (physostigmine, E2020, and Tacrine), all of which are to be cognitive enhancers, on the functional regional cerebral blood flow (rCBF) response were studied in young (5.9+/-1.8 years old) and aged (18.0+/-3.3 years old) monkeys under awake conditions using high-resolution positron emission tomography (PET). Under control condition, vibrotactile stimulation elicited increases in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in rCBF response was significantly lower in aged (115.8%) than that in young monkeys (139.9%). Regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, measured using [18F]-2-fluoro-2-deoxy-Dphysostigmine) were consistent with the data obtained by microdialysis. In contrast, the cognitive enhancers did not alter rCBF response to stimulation in young monkeys. The present results demonstrated that the functional change in rCBF response to the stimulation was induced during the aging process by impairment of the coupling mechanism between the neuronal activation and rCBF response. Furthermore, the observation that cognitive enhancers partly restored the functional rCBF response suggested that the coupling mechanism might be regulated via cholinergic neuronal transmission.

Acetylcholine↗

PubMed2000

Possible role of immune surveillance at the initial phase of metastasis produced by B16BL6 melanoma cells.

The relationship among the real-time trafficking of lung metastatic B16BL6 cells, metastatic potential, and the injected number of the cells was examined, since the smaller the number of tumor cells injected, the more clearly the immune defense may be observed. When 1x10(6) or 1x10(5) B16BL6 cells were injected into mice via the tail vein, both numbers of cells accumulated in the lung at a similar rate: there was an approximately 10-fold difference in the number of accumulated cells between the two doses. Elimination from the lung was not dependent on the cell number but on the proportion of accumulated cells. However, the injection of 1x10(4) cells resulted in lung accumulation less than one-tenth of that obtained with 1x10(5) cell injection. Metastasis was observed when 1x10(5) or 1x10(6) B16BL6 cells were injected, but not after injection of 1x10(4) cells. To clarify the roles of the immune defense system at the initial phase of metastasis, we challenged macrophage-depleted mice with 1x10(4) tumor cells. Treatment of mice with 2-chloroadenosine prior to the tumor cell challenge cancelled the suppression of not only metastasis but also the lung accumulation. Furthermore, the administration of 2-chloroadenosine following the tumor cell challenge had little effect on the metastatic potential. These results suggest that the immune surveillance whose action was obvious at the low dose of challenged tumor cells functions strongly at the initial phase but not at the advanced stages of the metastatic process, and that macrophages play an important role in the suppression of metastasis.

2-Chloroadenosine↗

PubMed2000

Ketamine decreased striatal [(11)C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: multiparametric PET studies combined with microdialysis analysis.

The effects of ketamine, a noncompetitive antagonist of NMDA receptors, on the striatal dopaminergic system were evaluated multiparametrically in the monkey brain using high-resolution positron emission tomography (PET) in combination with microdialysis. L-[beta-(11)C]DOPA, [(11)C]raclopride, and [(11)C]beta-CFT were used to evaluate dopamine synthesis rate, D(2) receptor binding, and transporter availability, respectively, in conscious and ketamine-anesthetized animals. Dopamine concentrations in the striatal extracellular fluid (ECF) were simultaneously measured by PET. Thirty minutes prior to PET scan, intravenous administration of ketamine was started by continuous infusion at a rate of 3 or 10 mg/kg/h. Ketamine infusion dose-dependently decreased [(11)C]raclopride binding, but induced no significant changes in dopamine concentration in the striatal ECF as measured by microdialysis at any dose used. In contrast, ketamine increased both dopamine synthesis and DAT availability as measured by L-[beta-(11)C]DOPA and [(11)C]beta-CFT, respectively, in a dose-dependent manner. These results suggest that the inhibition of glutamatergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability to the same extent, resulting in no apparent changes in ECF dopamine concentration as measured by microdialysis. It also suggests that the alteration of [(11)C]raclopride binding in vivo as measured by PET might not simply be modulated by the static synaptic concentration of dopamine.

Animals↗

PubMed2000

Lipopolysaccharide tolerance in relation to intrabronchial influx of neutrophils in the rat.

Lipopolysaccharide (LPS) is a potent chemotactic component for polymorphonuclear leukocytes (PMN, neutrophils). Since LPS tolerance was first described, many studies have been reported about the hyporesponsiveness in vitro corresponding to attenuating production of proinflammatory cytokines. We hypothesized that in vivo daily exposure to LPS stimuli impairs neutrophil accumulation in the rat airway. Interleukin 8 (IL-8) and/or CXC-chemokine, a neutrophil chemoattractant and activating cytokine, have been implicated as proinflammatory mediators in gram-negative respiratory tract infections. It is possible that the tolerance to LPS has occurred in relation to this chemoattractant cytokine production. To settle this issue, we examined whether the neutrophil count in bronchoalveolar lavage fluid (BALF) decreases after daily inhalation of Pseudomonas aeruginosa LPS into the rat airway. Repeated inhalation of LPS into the airway resulted in reduction in neutrophil recruitment. We measured rat CXC-chemokine (rat GRO/CINC1) levels in recovered BALF. There were noted reductions of rat GRO corresponding to the diminished neutrophil trafficking. We also confirmed that the HLA-DR positive lymphocyte number in BALF gradually increased after daily inhalation of LPS. These results suggest that continuous stimuli of LPS mitigate the accumulation of inflammatory cells in the airway by reducing chemokine production with a consequent change in the appearance of local inflammation to a chronic state.

Animals↗

PubMed2000

Surgical results for centrally-located early stage lung cancer.

BACKGROUND: With the increasing use of mass screening programs for lung cancer, and especially the use of sputum cytology, the incidence of roentgenographically occult lung cancer has been increasing. These occult cancers comprise mainly histologically centrally-located early stage lung cancers. This study examined the clinicopathologic characteristics and surgical results of centrally-located early stage lung cancer. RESULTS: From 1980 to 1998, there were 98 patients and 99 lesions of centrally-located early stage lung cancer resected. A total of 64 patients were detected by mass screening. Histologic examination revealed that 96 lesions were squamous cell carcinoma, and in these patients, there were 10 lesions of carcinoma in situ. The 5-year survival rate was 81.4% in all patients, and 88.9% in carcinoma in situ patients. In the postoperative follow-up period, a second lung cancer occurred in 13 patients. CONCLUSIONS: The surgical results for centrally-located early lung cancer were good. However, sometimes these cancers are accompanied by a second centrally-located primary lung cancer, so it is necessary to follow-up with sputum cytology to allow early detection of additional centrally-located lung cancer.

Adenocarcinoma↗

PubMed2000

Development of an automated synthesis apparatus for L-[3-11C] labeled aromatic amino acids.

We have developed an automated synthesis apparatus for L-[3-11C]-labeled aromatic amino acids by improved multi-enzymatic reactions. Use of a specially designed reaction vessel and of CH2Cl2 as a solvent has greatly simplified the overall operation, proving to be suitable for automated synthesis, and also has given better yields and higher specific activities than formerly reported values.

5-Hydroxytryptophan↗

PubMed2000

Development and evaluation of muscarinic cholinergic receptor ligands N-[11C]ethyl-4-piperidyl benzilate and N-[11C]propyl-4-piperidyl benzilate: a PET study in comparison with N-[11C]methyl-4-piperidyl benzilate in the conscious monkey brain.

The muscarinic cholinergic receptor ligands N-[(11)C]ethyl-4-piperidyl benzilate (4-EPB) and N-[(11)C]propyl-4-piperidyl benzilate (4-PPB) were developed and evaluated in comparison with N-[(11)C]methyl-4-piperidyl benzilate (4-MPB) in the conscious monkey brain using positron emission tomography (PET). Time-activity curves of [(11)C]4-EPB, unlike [(11)C]4-MPB, showed peaks within 91 min in regions rich in muscarinic receptors. [(11)C]4-PPB showed no specific binding even in the regions rich in these receptors. These observation demonstrated that increases in [(11)C]alkyl chain length could alter the kinetic properties of receptor ligands for PET.

Animals↗

PubMed2000

Preliminary study of the role of red foxes in Echinococcus multilocularis transmission in the urban area of Sapporo, Japan.

In order to assess the infection risk of alveolar echinococcosis among urban residents of Sapporo, the capital of Hokkaido, Japan, a survey was conducted on fox distribution in the urban area and on the prevalence of Echinococcus multilocularis among the foxes. The fox distribution, evaluated from fox footprints left on the snow in parks and woodlands, and from locations of fox carcasses recorded by the Sapporo municipality, was concentrated along the border of the urban area and in the southwestern part of the city, facing the mountain. Fox faeces were collected around active fox dens, and analysed by a coproantigen detection assay and parasite egg examination for the Echinococcus infection. Thirty-three out of 155 faeces were coproantigen positive. Coproantigen-positive faeces were collected from 11 den sites (57.9% of total den sites), and all except 1 were located in the urban fringe. A high intensity of taeniid eggs (> 100 eggs per 0.5 g) containing faeces were also collected in the 3 sites of them. Although Echinococcus infection in rodents was not observed from the necropsy of 23 rodents captured around active fox dens, arvicolid rodents, a suitable intermediate host for E. multilocularis, were captured in the urban fringe. Therefore, the urban fringe offers suitable conditions in which the life-cycle of E. multilocularis could be maintained. Prompt measures to control echinococcus infection should be taken, even in urban areas.

Animals↗

PubMed2000

Developmental changes of the vasculature in the periodontal ligament of rat molars: a scanning electron microscopic study of microcorrosion casts.

Vascularization of the periodontal ligament was examined in developing upper first molars of rats from 5 to 30 d after birth with light and scanning electron microscopy. Formation of the vascular network in the periodontal ligament (PDL) started with the beginning of root formation. The PDL vessels derived from the basal region of the tooth germ ran parallel to the long axis of the root and connected with the vascular network of the enamel organ at the cervical end. The boundary of these 2 networks was initially indistinct but became clearer with the progress of root formation. The PDL vessels further elongated longitudinally and connected with each other by lateral branches to form a coarse mesh. Other vessels derived from the alveolar bone via Volkman's canals also contributed to the vascular construction of the PDL. The vessels from the alveolar bone provided branches to the existing mesh of the PDL. Consequently, the vascular network of the PDL consisted of vessels from 2 sources: 1 derived from the basal region of the tooth germ, and the other from the alveolar bone. The density of the vascular network reduced with the progress of root formation, especially at the middle part of the root, but the mesh at the apical region maintained a basket-like structure.

Aging↗

PubMed2000

Dentoalveolar compensation in negative overjet cases.

The purpose of this study was to investigate dentoalveolar compensation in negative overjet cases. Eighty-eight adult females with either skeletal Class I or skeletal Class III jaw relationships were examined. Of the total, 44 cases showed anterior crossbite and the remaining 44 cases had normal incisor relationships. Four cephalometric parameters were measured: the sagittal jaw relationship, maxillary and mandibular incisor inclination, and the occlusal plane angulation. In the negative overjet cases, correlation analysis was performed between the skeletal and dental measurements. Stepwise discriminate analysis was carried out to separate the negative and normal overjet cases. Compensatory changes for sagittal jaw discrepancies in the negative overjet cases were statistically confirmed for both incisor inclination and occlusal plane angulation. However, the compensatory effects were weaker than in the normal overjet cases. The discriminate analysis successfully separated the normal and negative overjet cases, suggesting that negative overjet results from insufficient dentoalveolar compensation for variations in the sagittal jaw relationships.

Adaptation, Physiological↗

PubMed2000

Effect of argatroban on trinitrobenzene sulfonic acid-induced colitis.

BACKGROUND: Recent studies have suggested that heparin is effective for treatment of inflammatory bowel disease (IBD) and its various effects (in addition to the anticoagulant effect). We evaluated the effects of argatroban as an antithrombin drug on trinitrobenzene sulfonic acid (TNB)-induced colitis, an established model of IBD. METHODS: Rats were randomly assigned to four groups in which mini-osmotic pumps containing saline (TNB-S), argatroban (TNB-A), or 100 U/kg heparin (TNB-H) were intraperitoneally implanted. Three days after the pumps were implanted, TNB was infused via the anus, and colitis was induced. After 5 days, prothrombin time (PT), activated partial prothrombin time (APTT), antithrombin III (AT-III), platelet, fibrinogen, colonic wet weight, macroscopic damage score, histological score, mucosal myeloperoxidase activity and mucosal leukotrien B4 (LTB4) levels were compared among the four groups. RESULTS: The APTT was prolonged in the heparin treatment group but only slightly prolonged in the argatroban treatment group. The platelet count and the fibrinogen level were higher in the TNB-S group than in the healthy control group and the AT-III level was slightly lower in the TNB-S group than in the healthy control group and lower still in the TNB-H group. CONCLUSIONS: The colonic wet weight was similar among the four groups while the macroscopic damage score, histological score, mucosal myeloperoxidase activity and the mucosal LTB4 level were significantly decreased in the TNB-A and TNB-H groups. Argatroban, as well as heparin may be effective for treatment of TNB-induced colitis.

Analysis of Variance↗

PubMed2000

Gastric mucosal damage caused by monochloramine in the rat and protective effect of taurine: endoscopic observation through gastric fistula.

BACKGROUND AND STUDY AIMS: The mechanism of Helicobacter pylori-induced gastric mucosal injury is unknown, but H. pylori infection is conducive to accumulation in the stomach of monochloramine, a cytotoxic substance. The present study involved morphological investigation of the damaging effects of monochloramine on rat gastric mucosa, using endoscopic observations through a gastric fistula. The study also examined the protective effect of taurine against monochloramine-induced gastric mucosal lesions in rats. MATERIALS AND METHODS: The effects of monochloramine in rats were studied by administering the substance via a gastrostomy, which was then used to conduct a series of endoscopic observations. Local blood flow was measured using a laser Doppler method. Histological examination was carried out after 24 hours. Various monochloramine concentrations were used, and some animals were pretreated with taurine, a monochloramine scavenger, via the gastrostomy. RESULTS: Endoscopically, monochloramine was found to produce hemorrhagic mucosal erosions, mainly in the gastric body, in a time-dependent and concentration-dependent manner. Blood flow was decreased in advance of mucosal erosion. Taurine prevented mucosal injury by 30 mM monochloramine, the highest concentration tested. CONCLUSIONS: Although only the first 24 hours of mucosal injury were observed in the present study, the most likely mechanisms by which monochloramine caused injury to the gastric mucosa appeared to be both oxidative damage and a reduction in blood flow, impairing the mucosal defense mechanism.

Analysis of Variance↗

PubMed2000

Therapeutic effect of basic fibroblast growth factor on experimental pancreatitis in rat.

Basic fibroblast growth factor (bFGF) is one of the mitogens that facilitate endothelial proliferation and angiogenesis. This study was designed to examine the therapeutic effect of bFGF on experimental pancreatitis in rat. Edematous pancreatitis was induced by intraperitoneal injections of cerulein (50 microg/kg) at hourly intervals. BFGF (70 nmol/kg) was administered intraperitoneally after induction of pancreatitis. DNA synthesis of isolated pancreatic acinar cells of normal rats was determined as the uptake of 5-bromo-2'-deoxyuridine (BrdU) into the cells. Immunohistochemical staining of DNA synthesis in acinar cells during cerulein-induced pancreatitis was also examined with BrdU labeling in vivo technique. Cerulein administration increased serum amylase, lipase level, and wet weight of pancreatic tissue. Treatment with bFGF markedly ameliorated all these parameters. In primary culture system of isolated pancreatic acinar cells of normal rats, bFGF caused a dose-dependent increase in BrdU incorporation into DNA, showing an EC50 value of 0.8 nmol/L and a maximum response of 2.5-fold increase at a concentration of 400 nmol/L. bFGF treatment (70 nmol/kg) markedly increased BrdU labeling in the nucleus of acinar cells of the pancreatitis rats group in immunohistochemical examination when compared with control without bFGF treatment. Treatment with bFGF may represent a promising therapeutic concept for patients with acute pancreatitis.

Animals↗