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T Fukuda

Publications and source records attributed to T Fukuda.

At least 91 records · Page 5Linked to original sources
PubMed2001

Phorbol esters promote postsynaptic accumulation of Vesl-1S/Homer-1a protein.

We examined effects of phorbol esters on the amount and the subcellular distribution of the activity-regulated protein Vesl-1S/Homer-1a in cultured hippocampal neurons. Major Vesl-1S immunoreactivity (IR) was detected throughout neuronal somata under control conditions. Bath application of phorbol esters, PMA and PDBu resulted in the increase in the amount of Vesl-1S proteins and promoted punctate distribution of Vesl-1S IR at the cortical regions of the neuronal somata. Immunofluorescent observations using antisynaptophysin and anti-Vesl-1S antibodies, and electron microscopic observations, revealed that Vesl-1S accumulated at postsynaptic regions following PMA application. Membrane depolarization with high concentrations of external potassium also promoted the punctate distribution of Vesl-1S IR. These results demonstrate that phorbol-triggered reaction cascades result in the accumulation of Vesl-1S protein at postsynaptic regions, and suggest that these phorbol effects may mimic those caused by synaptic activities.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Expression of membrane-type 1 matrix metalloproteinase in rheumatoid synovial cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is thought to be a putative regulator of pro-gelatinase A (MMP-2) in the rheumatoid synovium. In this study, we examined the effects of IL-1beta, one of the inflammatory cytokines, on the expression of MT1-MMP and the activation of pro-MMP-2 using rheumatoid synovial cells. We also studied the effects of KE-298 (2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid), a new disease-modifying anti-rheumatic drug (DMARD), on MT1-MMP expression of rheumatoid synovial cells. Type B synovial cells (fibroblast-like synovial cells) were cultured with KE-298 (25-100 microg/ml) in the presence of IL-1beta for 48 h. Activation of pro-MMP-2 secreted from synovial cells was analysed by gelatin zymography. Reverse transcription-polymerase chain reaction (RT-PCR) methods were used to detect MT1-MMP mRNA. MT1-MMP protein expression on synovial cells was examined by anti-MT1-MMP immunoblot. An active form of MMP-2 was demonstrated in the culture media conditioned by IL-1beta-stimulated synovial cells. In addition, MT1-MMP mRNA and protein expression of rheumatoid synovial cells were increased by IL-1beta treatment. KE-298 blocked this IL-1beta-induced pro-MMP-2 activation and MT1-MMP expression, but did not affect IL-1beta-induced tissue inhibitor of metalloproteinase-2 (TIMP-2) secretion from rheumatoid synovial cells. These findings indicate that activation of rheumatoid synovial cells by IL-1beta results in the induction of MT1-MMP expression. Given that MT1-MMP promotes matrix degradation by activating pro-MMP-2, these results suggest a novel mechanism whereby cytokine may contribute to articular destruction in rheumatoid arthritis (RA). KE-298 may prevent this process by down-regulating MT1-MMP expression.

Antirheumatic Agents↗
PubMed2001

Evaluation of pancreatic secretion after administration of secretin: application of magnetic resonance imaging.

BACKGROUND: To evaluate pancreatic exocrine function, we measured the changes in T2 enhanced hydrograhic intensity on magnetic resonance (MR) images of the pancreas following an injection of secretin, which is representative of the changes in duodenal fluid volume. METHODS: The subjects were 10 patients with normal pancreatic function (N > 70% detected by using a pancreatic function diagnostant test) and 12 patients with hypo-function, including those with mild hypo-function (MH, 50-70%, six patients) and severe hypo-function (SH < 50%, six patients). RESULTS: In the N group, T2 enhanced intensity of the pancreas increased to a maximum value (more than 10% compared with baseline) within 5 min of stimulation, then gradually decreased. No significant difference in the response was observed between the head and body of the pancreas. Changes in the MH group were similar to those of the N group. In contrast, significantly lower changes in T2 enhanced intensity were observed in SH group, relative to both the N and MH group (P < 0.05). The amount of secretin-induced increase in duodenal fluid after 16 min was not significantly different among the three groups. Furthermore, an evaluation of the residual pancreatic tissue after a pancreatoduodenectomy was also feasible. CONCLUSIONS: Our results indicate that the MR-secretin test is useful for the evaluation of severe pancreatic exocrine dysfunction. The diagnostic test is simple, direct and non-invasive.

Adult↗
PubMed2001

Neurotoxicity of MPTP.

After the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we acquired a good animal model of Parkinson's disease. The extraordinary recent growth in knowledge using MPTP parkinsonism has fostered increased understanding of Parkinson's disease. In the present paper, the discovery of MPTP and the biochemical, pathological, and clinical findings of MPTP parkinsonism are first reviewed briefly. Next, using MPTP parkinsonism, unresolved issuses such as the apoptosis of MPTP, levodopa toxicity, and neuroprotective effects of monoamine oxidase inhibitors or dopamine agonists are discussed. Finally, environmental factors such as the etiology of Parkinson's disease are examined. Some genetic factors that lead to familial Parkinson's disease have recently been reported, but most cases of Parkinson's disease are sporadic. Recent epidemiological evidence emphasizes an etiological relation of 18th and 19th century industrialization to Parkinson's disease. Man-made toxins, such as industrial chemicals and herbicides/pesticides, have been suggested to increase the risk of developing Parkinson's disease. I would like to highlight the significance of re-examination of environmental factors in the etiology of Parkinson's disease.

Animals↗
PubMed2001

Ovarian fibrosarcoma producing multiple cytokines.

A case of ovarian fibrosarcoma producing multiple cytokines is presented. The tumor occurred in the left ovary of a Japanese woman with epigastralgia, remittent fever, leukocytosis and slight thrombocytosis with moderate increase of mast cells in bone marrow, but lack of hormonal abnormality. The resected tumor of the ovary was well encapsulated and it was composed of spindle-shaped tumor cells and scattered tubules with marked mast cell infiltration. The tumor recurred in the pelvic cavity 14 months later, accompanied by similar signs and symptoms as occurred with the primary tumor. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were elevated. The recurrent tumor showed similar histological findings to those of the primary tumor, except for lack of tubules. Tumor cells revealed a focally positive immunoreaction for vimentin, IL-6 and TNF-alpha and alpha-inhibin. Reverse transcription-polymerase chain reaction using total RNA obtained from the recurrent tumor demonstrated mRNA expression of IL-6, IL-10, TNF-alpha and stem cell factor. This is a rare case of ovarian fibrosarcoma producing multiple cytokines, resulting in atypical clinical findings.

Cytokines↗
PubMed2001

Compositional and functional changes of pulmonary surfactant in a guinea-pig model of chronic asthma.

Recent studies have found that severe surfactant dysfunction occurs during an asthma attack, but the changes in surfactant in a guinea-pig model of chronic asthma have not been studied. We therefore analysed the surfactant recovered from guinea-pigs after repeated inhalation of ovalbumin to see if the surfactant recovered from chronic asthmatic lungs would be intrinsically altered. Guinea pigs immunized through repeated inhalation of aerosolized ovalbumin (OA) were exposed to the antigen once a week for a month. Twenty-four hours after the last challenge the alveolar wash was recovered. We calculated saturated phosphatidylcholine (Sat-PC) and total protein (TP) pool sizes in alveolar spaces. Surfactant subtype conversion of large aggregate surfactant (LA) to small aggregate surfactant was studied in vitro by means of the surface area cycling technique. The phospholipid composition of LA was analysed by thin layer chromatography and the surface activity of LA was also determined. We found decreased surfactant pool sizes, decreased ratio of Sat-PC to TP in alveolar lavages in asthma groups, and surface activity of the surfactant recovered from asthmatic lungs to be inferior to that of the controls. Accelerated surfactant subtype conversion in vitro was also noted in the lungs of asthmatic animal models. In addition, the changes in phospholipid compositions which were similar to the pattern of acute lung injury suggested that alveolar inflammation might be involved in the pathogenesis of chronic asthma. These results indicate that surfactant is intrinsically abnormal in chronically asthmatic lungs.

Analysis of Variance↗
PubMed2001

Follow-up study of coronary artery bypass grafting in patients with Kawasaki disease.

BACKGROUND: The purpose of this study was to assess the long-term clinical outcome of coronary artery bypass grafting in pediatric patients with Kawasaki disease. METHODS: Six patients (mean age, 9.3 +/- 1.6 years) underwent coronary artery bypass grafting between September 1985 and December 1992. The number of bypass grafts placed was 1 to 2 per patient (mean 1.3 +/- 0.5). The left internal mammary artery (IMA) was used as a bypass graft in 3 patients, bilateral IMA in 1, and saphenous vein in 3. All patients underwent postoperative evaluations after 1 month and between 5 and 10 years. RESULTS: Follow-up ranged between 9 and 16 years (mean 12.6 +/- 2.7 years). Stress myocardial scintigraphy identified 2 patients with transient ischemia, one of whom died suddenly after 16 postoperative years. Coronary angiography demonstrated that the grafts of 5 patients were patent at both the short- and long-term follow-up. However, in 1 patient, the IMA that was grafted to the diagonal artery was occluded 1 month after surgery. Five survivors are in good health, without clinical angina. CONCLUSIONS: We consider that coronary revascularization with bilateral IMA grafts may provide a more favorable prognosis in patients with severe Kawasaki coronary artery disease. Stress myocardial scintigraphy and echocardiography can be used effectively to follow such patients.

Adolescent↗
PubMed2001

Continuous perfusion of pulmonary arteries during total cardiopulmonary bypass favorably affects levels of circulating adhesion molecules and lung function.

OBJECTIVES: Lung injury is a serious complication of cardiopulmonary bypass in infants with congenital heart disease and pulmonary hypertension. Cessation of blood flow in the pulmonary arteries during cardiopulmonary bypass is known to provoke lung dysfunction. We assessed the effect of continuous pulmonary perfusion on circulating adhesion molecules and on lung function. METHODS: Fourteen infants with congenital heart disease and pulmonary hypertension were enrolled in the study. During total cardiopulmonary bypass, 8 patients underwent continuous perfusion of the pulmonary arteries (perfusion group), and the remaining 6 patients did not (control group). Plasma levels of circulating intercellular adhesion molecule 1, soluble granule membrane protein 140, and sialyl Lewis(x) and PaO (2)/fraction of inspired oxygen ratios were measured before commencement and serially for 24 hours after termination of bypass. RESULTS: Plasma levels of circulating intercellular adhesion molecule 1 decreased significantly at the termination of bypass in both groups but returned to prebypass levels immediately in the control group, whereas in the perfusion group the values remained significantly less than those before bypass. Plasma levels of soluble granule membrane protein 140 in the control group were significantly higher at 6 and 12 hours after bypass than levels before bypass, whereas in the perfusion group the values remained at the prebypass level throughout the postbypass period. Trends of plasma levels of sialyl Lewis(x) were alike in both groups. PaO (2)/fraction of inspired oxygen ratios in the control group decreased significantly from 6 hours after bypass, whereas values in the perfusion group remained at the prebypass value throughout the postbypass period. CONCLUSIONS: This study suggests that in infants having congenital heart disease and pulmonary hypertension, continuous pulmonary perfusion during total cardiopulmonary bypass minimizes ischemic insult and neutrophil-endothelial interaction mediated by adhesion molecules in the pulmonary microvessels.

Analysis of Variance↗
PubMed2001

Recruitment of nonexpanded polyglutamine proteins to intranuclear aggregates in neuronal intranuclear hyaline inclusion disease.

Recruitment of polyglutamine-containing proteins into nuclear inclusions (NIs) was investigated in neuronal intranuclear hyaline inclusion disease (NIHID). Some polyglutamine-containing proteins, ataxin-2, ataxin-3, and TATA box binding protein (TBP), as well as unidentified proteins with expanded polyglutamine tracts were recruited into NIs with different frequencies. Ataxin-3 was incorporated into most of the NIs and disappeared from its normal cytoplasmic localization, whereas only a small fraction of NIs contained ataxin-2 and TBP. The consistent presence of ataxin-3 in NIs could reflect a biological feature of wild-type ataxin-3, which is translocated into the nucleus under pathological conditions and participates in the formation of aggregates. Ataxin-2 also accumulated in the nucleus, but was not necessarily incorporated into NIs, suggesting that transport of these cytoplasmic proteins into the nucleus and their recruitment into NIs are not wholly explained by an interaction with a polyglutamine stretch and must be regulated in part by other mechanisms. The prevalence of ubiquitin-immunopositive NIs was inversely correlated to neuronal loss in all cases examined. This correlation could be explained if NI formation is a protective mechanism involving the ubiquitin-proteasome pathway. This hypothesis is supported by the finding that the polyglutamine epitope in the center of NIs was surrounded by ubiquitin.

Adult↗
PubMed2001

The effects of 30% and 60% xenon inhalation on pial vessel diameter and intracranial pressure in rabbits.

UNLABELLED: Xenon may increase cerebral blood flow and intracranial pressure (ICP). To evaluate the effects of xenon on brain circulation, we measured pial vessel diameter changes, CO(2) reactivity, and ICP during xenon inhalation in rabbits. Minimum alveolar anesthetic concentration (MAC) for xenon was established in rabbits (n = 6). By using a cranial window model, pial vessel diameters were measured at 30% and 60% xenon inhalation and in time control groups (n = 15). ICP, mean arterial blood pressure, and heart rate were recorded during 30% and 60% xenon inhalation (n = 5). Pial vessel diameters were measured during hypocapnia and hypercapnia conditions in 60% Xenon and Control groups (n = 14). MAC for xenon was 85%. Xenon (0.35 and 0.7 MAC) dilated the arterioles (10% and 18%, respectively) and venules (2% and 4%, respectively) (P < 0.05). Dilation of arterioles was more prominent than that of venules. ICP, mean arterial blood pressure, and heart rate did not change during xenon inhalation. No difference in CO(2) reactivity was observed between Xenon and Control groups (P = 0.79). Sixty percent xenon (0.7 MAC) dilated brain vessels, but venule changes were small. Xenon did not increase ICP and preserved CO(2) reactivity of the brain vessels. IMPLICATIONS: Xenon might increase cerebral blood flow; however, 0.7 minimum alveolar anesthetic concentration xenon preserved both low intracranial pressure and CO(2) reactivity of the cerebral vessels in the normal rabbit.

Administration, Inhalation↗
PubMed2001

The residual effects of hemorrhagic shock on pain reaction and c-fos expression in rats.

UNLABELLED: To investigate the residual effects of hemorrhagic shock on pain reaction and c-fos expression, we performed formalin tests after hemorrhage and reinfusion in rats. Twenty adult male Sprague-Dawley rats were divided into Control (n = 10) and Postshock (n = 10) groups. The mean blood pressure of the Control group was 100-120 mm Hg, and that of the Postshock group was kept at 50-60 mm Hg for 30 min by draining blood. After 15 min of returning mean blood pressure to normal levels in the Postshock group, 10% formalin (3.7% formaldehyde solution, 100 microL) was injected into the left rear paw of both groups. Nociceptive behaviors were observed for 1 h after the formalin injection. The rats were killed at 2 h after the formalin injection, and the lumbar spinal cord was then stained for c-fos immunohistochemistry by using the avidin-biotin-peroxidase method. Animals in the Postshock group showed considerably less nociceptive behavior than those in the Control group. C-fos expression in the deep layer (IV-VI) of the spinal cord was significantly less in the Postshock group. In conclusion, decreases of nociceptive behaviors and c-fos expression were observed under normotensive conditions after hemorrhagic shock. The mechanisms governing these reactions remain unclear. IMPLICATIONS: Formalin tests were performed after hemorrhage and reinfusion in rats. A stress-induced analgesia was observed under normotensive conditions after hemorrhagic shock. The mechanisms remain unclear.

Animals↗
PubMed2001

New technique for application of fibrin sealant: rubbing method devised to prevent cerebrospinal fluid leakage from dura mater sites repaired with expanded polytetrafluoroethylene surgical membranes.

OBJECTIVE: The effectiveness of a strong, pressure-tight method for fibrin sealant application was experimentally and clinically evaluated, using expanded polytetrafluoroethylene (ePTFE) surgical membranes. METHODS: Two application methods were examined in two groups. For Group 1, 1 ml each of Solutions A and B was simply sprayed over the surface (spray method). For Group 2, a small amount of Solution A was rubbed into the sutured site and then Solutions A and B were sprayed over the surface (rubbing method). In the experimental study, a moment pressure elevation test and a continuous stepwise pressure elevation test were performed for both groups. The clinical study was conducted using 350 patients undergoing craniotomies. The ePTFE surgical membrane was used for 180 patients but not the other 170 patients. RESULTS: In the experimental study, the bursting pressures were 51.4 +/- 13.0 cm H2O for Group 1 and 129 +/- 35.0 cm H2O for Group 2 in the moment pressure elevation test and 27.0 +/- 6.7 cm H2O and 100 +/- 31.9 cm H2O, respectively, in the continuous stepwise pressure elevation test. The sealing effect was significantly greater for Group 2 than for Group 1 in both tests (P < 0.001). In the clinical study using ePTFE surgical membranes, the rubbing method significantly reduced the incidence of postoperative cerebrospinal fluid leakage (1.4%), compared with the spray method (18.3%), when external decompression was not concomitantly used (P < 0.01). CONCLUSION: The sealing effect of fibrin sealant on cerebrospinal fluid leakage was significantly greater with the rubbing method than with the spray method. The strong sealing effect obtained with the rubbing method is thought to result from firm linkage between the ePTFE surgical membrane and the fibrin sealant and also from fibrin being formed even in needle holes and spaces in the sutured site.

Adolescent↗
PubMed2001

A549 cells can express interleukin-16 and stimulate eosinophil chemotaxis.

Alveolar epithelial cells produce many types of chemokines such as regulated on activation, normal T cells expressed and secreted (RANTES), eotaxin induced by interleukin (IL)-1 beta, or tumor necrosis factor (TNF)-alpha and may contribute to allergic disease by recruiting eosinophils. However, identification of the eosinophil chemotacic activity (ECA) release from A549 cells, an alveolar type II cell line, has not yet been completed. Recently, IL-16 was also reported to be a potent chemotactic stimulus for CD4(+) T lymphocytes and eosinophils in asthma and other pulmonary diseases. To test the possibility that alveolar epithelial cells produce IL-16, we analyzed RNA and culture supernatant from A549 cells by reverse transcription/ polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The release of ECA from A549 cells was assessed using a blind-well chemotactic chamber. IL-16 release was increased in a concentration-dependent manner by stimulation with IL-1 beta or TNF-alpha. A549 cells also expressed IL-16 messenger RNA. The combination of IL-4 and IL-1 beta or TNF-alpha had an additive effect on IL-16 production. The release of ECA was induced by IL-1 beta or TNF-alpha in a dose-dependent manner. The combination of these cytokines had a greater effect than one alone. The blockade of eotaxin and IL-16 caused 70% inhibition of ECA, but anti-RANTES antibodies only caused 30% inhibition and anti-IL-8 antibodies failed to affect inhibition. These findings suggest a role for chemokines released by alveolar epithelial cells in the recruitment of eosinophils into the lung in pulmonary disorders such as asthma and interstitial lung diseases, and suggested that eotaxin and IL-16 are potent and effective eosinophil chemoattractants.

Base Sequence↗
PubMed2001

Iontophoretic pulsatile transdermal delivery of human parathyroid hormone (1-34).

Iontophoretic pulsatile transdermal delivery of hPTH(1-34) was examined in Sprague-Dawley (SD) rats, hairless rats and beagle dogs. Application for 60 min (200 microg; 0.1 mA cm(-2)) showed current-responsive increases in serum hPTH(1-34) levels in all the animals. In SD rats, the area under the curves of serum hPTH(1-34) levels (AUCs) were proportional to the doses (40, 120, 200, 400 and 1000 microg) and current densities (0.05, 0.1 and 0.15mA cm(-2)) applied. The absorption rates per 200-microg dose, calculated by a deconvolution method, were 6.7, 2.4 and 3.7 microg h(-1) for SD rats, hairless rats and beagle dogs, respectively. These values correlated well with the ratios of the skin porosity to the dermal thickness reported for these animals, which are believed to represent the reciprocal of the electrical resistance of the aqueous channels formed by the hair follicles. From this correlation, we suggested that absorption of hPTH(1-34) occurs mainly via the hair-follicle route, and that the absorption rate in man might be intermediate between those in hairless rats and beagle dogs. Three-fold repetitions of 30 min current with various rest intervals produced current-responsive triple pulses in serum hPTH(1-34) levels in SD rats. Seven-fold repetitions of current also produced similar current-responsive pulsatile serum hPTH(1-34) levels. However, peak serum hPTH(1-34) levels tended to decrease gradually after the fourth current application, possibly due to consumption of the electrodes, suggesting that three-fold repetitions of current might be optimal. These findings suggest that this iontophoretic administration system could create a repeated-pulsatile pattern of serum hPTH(1-34) levels without the necessity for frequent injections, and may be useful for the treatment of osteoporosis with hPTH(1-34).

Absorption↗
PubMed2001

Testicular germ cell apoptosis in Bcl6-deficient mice.

Bcl6 protein has been detected in testicular germ cells, mainly spermatocytes, of normal mice, but its physiological role is largely unknown. The number of spermatozoa in the cauda epididymis of adult Bcl6-deficient (Bcl6-/-) mice is lower than that of Bcl6+/+ mice. We have found numerous apoptotic spermatocytes at the metaphase I stage with induction of Bax protein in adult Bcl6-/- testes. Developmentally, the incidence of germ cell apoptosis of Bcl6-/- mice was similar to that of Bcl6+/+ mice until six weeks of age and increased after eight weeks of age. The incidence of apoptosis in heterozygous Bcl6+/- mice was also higher than that of Bcl6+/+ mice. Since the activated form of p38 MAP kinase was detected in spermatocytes of adult Bcl6-/- mice, the germ cell apoptosis may be induced by stressors. Treatment of testes of adult Bcl6+/+ mice with a mild hyperthermia resulted in germ cell apoptosis predominantly in metaphase I spermatocytes with induction of Bax protein and activation of p38 MAP kinase and this apoptosis mimics that in adult Bcl6-/- mice. Thus, Bcl6 may play a role as a stabilizer in protecting spermatocytes from apoptosis induced by stressors.

Animals↗