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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 253 records · Page 14Linked to original sources
PubMed1999

Brain metastasis from hepatocellular carcinoma after radical hepatectomy.

Brain metastasis from hepatocellular carcinoma (HCC) is a rare, yet perplexing problem in patients with cancer. We report on 5 patients with metastasis of HCC to the brain after radical hepatectomy. Intrahepatic recurrence occurred in 3 patients, and distant metastasis to sites other than the brain was observed in 3 patients (lung, 2; bone, 1). The symptoms for brain metastasis included headache, hemiparesis, and vomiting. Hemorrhage was found in 4 of 5 patients. All patients had a single nodular lesion in the brain. The alpha-fetoprotein levels were more than 10,000 ng/ml in 4 patients. Two patients underwent surgical resection, 1 received cranial irradiation, and 2 were administered corticosteroids. The interval between diagnosis of the primary cancer and detection of brain metastasis ranged from 2 to 54 months. The mean survival period was only 3 months after diagnosis of brain metastasis. All 5 patients died of neurologic causes. Because no effective treatment for brain metastasis from HCC is available, further study is needed.

Adult↗
PubMed1999

[A mechanism for the anti-inflammatory effect of nedocromil; inhibition of both adhesion molecule expression on eosinophils and endothelial cells, and eosinophil chemotactic activities].

The accumulation of eosinophils in the airway is one of the characteristics seen in patients with bronchial asthma. One of the newly developed anti-asthma drugs (controller), nedocromil sodium (nedocromil) is known to suppress the influx of eosinophils into allergic lesions. However, little is known about this mechanism. Therefore, in this report we investigated the effects of nedocromil on Mac-1 expression on PAF-stimulated eosinophils, and adhesion molecule expression on endothelial cells stimulated by either IL-1 beta or IL-4. We also investigated the eosinophil chemotaxis. A significant suppression of the Mac-1 expression on PAF-induced eosinophils was observed at both concentrations of 10(-5) and 10(-7) M of nedocromil. The expression of adhesion molecules, particularly ICAM-1 and E-selectin, on IL-1 beta-stimulated human umbilical vascular endothelial cells (HUVEC) was significantly suppressed at these concentrations, whereas the VCAM-1 expression was not changed. No significant suppression of VCAM-1 expression on IL-4-stimulated HUVEC was observed, although there was a tendency of suppression at these concentrations. On the other hand, the expression of the E-selectin molecule was significantly suppressed by nedocromil even under resting (non-stimulated) condition. PAF-induced eosinophil chemotactic activities were also suppressed at these concentrations in a dose-dependent manner. These results suggested that nedocromil suppressed the influx of eosinophils to inflammatory lesions by inhibiting not only the expression of the Mac-1 on eosinophils and of E-selectin and ICAM-1 molecules on HUVEC, but also the eosinophil chemotactic activities.

Anti-Asthmatic Agents↗
PubMed1999

[Effect of rush immunotherapy (RIT) on Hymenoptera allergy].

In our country approximately forty people die every year from anaphylaxis caused by hymenoptera stings. Between 1988 and 1996, 48 patients, who had experienced a systemic reaction to hymenoptera sting and were proved to have specific IgE antibodies to wasp, yellow or both (RAST score > or = 2), received rush immunotherapy (RIT) using venom extracts in our hospital. Fifteen patients had re-sting after RIT. Fourteen out of the 15 patients showed only local reaction to the hymenoptera re-sting and one patient had mild generalized symptoms. Although one patient showed mild generalized uriticaria during RIT, no adverse reaction occurred during and after RIT in the other subjects. Follow-up studies on the titers of serum total IgE antibodies and hymenoptera specific IgE and IgG4 antibodies revealed that total and specific IgE antibodies transiently increased one month after RIT and returned to their baseline values by 6 months after RIT, while specific IgG4 antibodies continued to gradually increase up to al least 3 years after RIT. These results demonstrates that RIT is effective in prevention of a systemic reaction to hymenoptera re-sting and an increase in the titer of hymenoptera specific IgG4 antibodies may at least partly explain the efficacy of RIT.

Adult↗
PubMed1999

Quantification of neuromodulin (GAP-43, B-50) and synapsin I in rat striata.

We reported previously that phosphorylated neuromodulin and phosphorylated synapsin I content increased in the striata of amphetamine-sensitized rats; however, the neuronal pathways responsible for the increase were unclear. In the present study, changes in neuromodulin and synapsin I content resulting from the manipulation of lesions were quantified to elucidate the responsible pathways. Nerve terminals originating in the corticostriatal pathway, those from the nigrostriatal pathway and those from interneurons in the striatum, were impaired by unilateral cortical ablation, 6-hydroxydopamine (6-OHDA) treatment and kainic acid injection into the striatum, respectively. Neuromodulin and synapsin I content in the ipsilateral striatum after unilateral ablation of the frontal cortex decreased by 51 and 31%, respectively. The impairment of dopaminergic terminals by 6-OHDA reduced the neuromodulin content by 22%; however, no significant alteration was observed in the synapsin I content as the result of 6-OHDA treatment. The injection of kainic acid did not cause the content of either protein to decrease. These results suggest that corticostriatal nerve terminals possess a large part of the total neuromodulin and almost all the synapsin I in the striatum. Therefore, the increase in phosphorylated neuromodulin induced by repeated treatment with amphetamine may occur in corticostriatal glutamatergic terminas and/or nigrostriatal dopaminergic terminals. On the other hand, the increase in phosphorylated synapsin I may preferentially occur in the corticostriatal glutamatergic terminals.

Animals↗
PubMed1998

Quantitative analysis of GABAergic neurons in the mouse hippocampus, with optical disector using confocal laser scanning microscope.

The numerical densities (NDs) of glutamic acid decarboxylase (GAD) 67 immunoreactive (IR) neurons in the mouse hippocampus were estimated according to the optical disector method using a confocal laser scanning microscope (CLSM), and the cell sizes of disector-counted neurons were measured. Particularly, we focused on the dorsoventral differences of the NDs and cell sizes in individual subdivisions and layers. The NDs of GAD67-IR neurons were larger at the ventral level than at the dorsal level in most subdivisions and layers, except in the stratum pyramidale (SP) of the CA1 region and stratum radiatum (SR) of the CA3 region. In the whole hippocampus, the ND of GAD67-IR neurons was 5.7+/-0.2x103/mm3 at the dorsal level, and 7.3+/-0.3x103/mm3 at the ventral level. The laminar differences showed that the NDs of GAD67-IR neurons in the principal cell layers were generally larger than those in the dendritic layers in each subdivision. The ND of GAD67-IR neurons was largest in the SP of the CA1 region at the dorsal level (13.5+/-0.9x103/mm3), and smallest in the molecular layer (ML) of the dentate gyrus (DG) at the dorsal level (1.7+/-0.2x103/mm3). The mean cell sizes of GAD67-IR neurons also showed prominent dorsoventral and laminar differences. In the CA3 region, the mean cell size of GAD67-IR neurons was smaller at the dorsal level than at the ventral level, while in the DG, it was larger at the dorsal level than at the ventral level. On the other hand, the mean cell size of GAD67-IR neurons in the CA1 region showed no significant dorsoventral difference. In the whole hippocampus, the mean cell size of GAD67-IR neurons was slightly smaller at the dorsal level (somatic profile area 149.2+/-2.5 microm2) than at the ventral level (154.2+/-2.9 microm2). The laminar differences showed that the mean cell sizes of GAD67-IR neurons in the principal cell layers were generally larger than those in the dendritic layers in each subdivision. The mean cell size of GAD67-IR neurons was largest in the SP of the CA3 region at the ventral level (180.7+/-8.7 microm2), and smallest in the stratum lacunosum-moleculare (SLM) of the CA3 region at the dorsal level (115.9+/-7.9 microm2). The cell size distributions in individual layers revealed that GAD67-IR neurons were roughly classified into two subgroups. The composition of these subgroups suggested the heterogeneity of GAD67-IR neurons in the mouse hippocampus in view of cell size

Animals↗
PubMed1998

Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells.

The effect of cytochrome P-450 3A (CYP3A) substrates (erythromycin, midazolam) and an inhibitor (ketoconazole) on P-glycoprotein-mediated transport was studied in Caco-2, the human colon adenocarcinoma cell line expressing various functions of differentiated intestinal epithelial cells. The involvement of P-glycoprotein in the transport of these drugs was also examined. The basal-to-apical transport of rhodamine 123, a P-glycoprotein substrate, was inhibited by erythromycin, midazolam and ketoconazole, as well as by P-glycoprotein inhibitors such as verapamil. The apical-to-basal transport of rhodamine 123 was increased by these drugs. The transepithelial transport of erythromycin and midazolam, but not of ketoconazole, was much greater from the basal to apical side than from the apical to basal side. The inhibitory effect of verapamil was observed on the basal to apical transport of erythromycin, but not on midazolam and ketoconazole transport. In conclusion, erythromycin, midazolam and ketoconazole could interact with P-glycoprotein-mediated transport, and P-glycoprotein could be, at least in part, involved in the transport of erythromycin, but not of midazolam and ketoconazole, in the intestinal epithelia.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1998

Correlation between methylation status of the p16/CDKN2 gene and the expression of p16 and Rb proteins in primary non-small cell lung cancers.

In order to clarify the frequency of p16 gene inactivation and its relationship with Rb expression, immunohistochemical analysis of p16 and Rb proteins was carried out on 82 paraffin-embedded sections of primary non-small cell lung cancers (NSCLCs). From immunohistochemical results, abnormal p16 expression was observed in 66% of NSCLCs, 80% in squamous cell carcinomas and 46% in adenocarcinomas. An inverse correlation between p16 and Rb expressions was noted. Moreover, the methylation status of the p16 gene was investigated by the methylation-specific polymerase chain reaction (MS-PCR) using 29 frozen samples of NSCLCs. MS-PCR revealed the methylation of the p16 gene in 10(34%)of 29 NSCLCs. All NSCLCs exhibiting methylation exhibited abnormal p16 expression and were positive for Rb. In NSCLCs, no difference in methylation status was observed with respect to clinico-pathological characteristics including histological subtype and tumor stage. Our results demonstrate that abnormality of p16 expression is frequent in primary NSCLCs and methylation of the promoter of the p16 gene occurs in 34% of primary NSCLCs, which might play a significant role in the inactivation of the p16 gene.

Adenocarcinoma↗
PubMed1998

GABAergic axon terminals at perisomatic and dendritic inhibitory sites show different immunoreactivities against two GAD isoforms, GAD67 and GAD65, in the mouse hippocampus: a digitized quantitative analysis.

Glutamic acid decarboxylase (GAD), the gamma-aminobutyric acid (GABA)-synthetic enzyme, consists of two isoforms, GAD67 and GAD65. Although distributions of the two GAD isoforms at the somatic level are known to be heterogeneous among different subpopulations of GABAergic neurons, those at the synaptic level have not been investigated. In order to analyze quantitatively the two GAD-isoform immunoreactivities in axon terminals, we combined confocal laser scanning microscopy with digitized image analysis to measure the gray levels of immunofluorescent signals for the two GAD isoforms in a large number of individual boutons in each hippocampal and dentate layer of the mouse. Synaptic boutons exhibited lamina-specific immunoreactivities against the GAD isoforms. Boutons in the principal cell layers (stratum pyramidale of the hippocampus proper and the granule cell layer of the dentate gyrus) showed more intense immunoreactivity against GAD67 than those in the dendritic layers (strata lacunosum-moleculare, radiatum, and oriens of the hippocampus proper and the molecular layer of the dentate gyrus). By contrast, boutons in the dendritic layers showed more intense immunoreactivity against GAD65 than those in the principal cell layers. Such differential distributions could be correlated to the GAD-isoform immunoreactivities in the axon terminals originating from parvalbumin-containing neurons, a particular subpopulation of hippocampal GABAergic neurons mainly innervating the perisomatic domain of principal neurons. In addition to previously reported physiological and pharmacological differences between the GABAergic synapses on perisomatic domain and those on distal dendrites, the present results suggest a functional differentiation of GABAergic synapses between these two inhibitory sites.

Animals↗
PubMed1998

Coordinate expression of L1 and 6B4 proteoglycan/phosphacan is correlated with the migration of mesencephalic dopaminergic neurons in mice.

Mesencephalic dopaminergic (DA) neurons of mice are generated from embryonic day 10 to 12 (E10-12) in the ventricular zone of the mesencephalon. They first migrate toward the ventral mesencephalon, and then turn laterally, or tangentially, in the basal part of the mesencephalon. With immunohistochemical analysis of E10-E15 ICR mice, we found that cell adhesion molecule L1 was transiently expressed on the median part of tangential fibers coincident with the lateral migration of DA neurons from E11 to E13, when neurons move along the tangential fibers toward their final destinations: the reticular formation, the substantia nigra pars compact, and the ventral tegmental area. While L1 expression was not observed in DA neurons, they expressed a chondroitin sulfate proteoglycan, 6B4 proteoglycan/phosphacan, which has been shown to bind to L1/Ng-CAM in vitro. These results suggest that the heterophilic interaction between 6B4 proteoglycan on the neurons and L1 on the fibers is involved in the lateral migration of mesencephalic DA neurons in mice.

Animals↗
PubMed1998

Enzymatic amplification and expression of bovine interleukin-1 receptor antagonist cDNA.

cDNA generated from lipopolysaccharide-stimulated bovine peripheral blood mononuclear cells was used to amplify and clone the bovine interleukin-1 receptor antagonist (IL-1ra) using primers derived from semi-conserved regions between human and mouse IL-1ra sequences. 5' and 3' terminal sequences of bovine IL-1ra were amplified by 5' and 3' rapid amplification of cDNA ends. The deduced amino acid sequence of bovine IL-1ra demonstrated 80%, 78%, 78%, 77% and 76% homology with human, mouse, rat, rabbit and equine sequences, respectively. Recombinant bovine IL-1ra produced in Escherichia coli suppressed the growth inhibitory activity of bovine IL-1beta on A375 cells in a dose-dependent manner, indicating that the present bovine IL-1ra cDNA encodes biologically active proteins.

Amino Acid Sequence↗
PubMed1998

Binding and functional properties of four extrinsic proteins of photosystem II from a red alga, Cyanidium caldarium, as studied by release-reconstitution experiments.

Photosystem II (PSII) from a red alga, Cyanidium caldarium, contains four extrinsic proteins of 33, 20, and 12 kDa and cytochrome (cyt)c550 [Enami, I., et al., (1995) Biochim. Biophys. Acta 1232, 208-216]. The binding and functional properties of these four proteins in the red algal PSII were studied by release-reconstitution experiments. Of the four components, the 33 kDa protein binds to PSII completely by itself, and the 20 kDa protein binds to a level 61% of that in native PSII in the absence of other proteins. In contrast, cyt c550 and the 12 kDa protein cannot bind to PSII efficiently by themselves; their effective binding requires the other three extrinsic proteins. In particular, a strong interaction was observed between cyt c550 and the 12 kDa protein, and a weaker interaction was observed between cyt c550 and the 20 kDa protein. While binding of the 33 kDa protein alone or cyt c550 and the 12 kDa protein in the presence of the 33 and/or the 20 kDa protein generally enhanced oxygen evolution, binding of the 20 kDa protein did not. Oxygen evolution was strongly dependent on Ca2+ and Cl- in the absence of cyt c550 and the 12 kDa protein, suggesting that these two proteins have functions similar to those of the 23 and 17 kDa proteins in higher plant PSII. From these results, we propose that the unique 20 kDa extrinsic protein found only in the red algal PSII functions in maintaining the proper binding of cyt c550 and the 12 kDa protein but is not involved directly in oxygen evolution. The binding and functional properties of these four proteins were compared with those of the three extrinsic proteins found in cyanobacterial and higher plant PSII in an evolutionary point of view.

Cytochrome c Group↗
PubMed1998

Submucosal gastric cancer with lymph node metastasis.

BACKGROUND AND OBJECTIVES: The intraoperative assessment of lymph node metastasis of gastric cancer remains difficult and the characteristics of recurrence after gastrectomy are not well known regarding submucosal cancer. METHODS: We examined 452 patients with submucosal gastric cancer and compared the clinicopathologic features as well as recurrence patterns between the 71 cases with lymph node metastasis (group I) and the 381 without it (group II). RESULTS: The mean tumor sizes were 44.8 and 33.5 mm, respectively (P < 0.01). The incidences of lymphatic invasion and vascular invasion were 91.5% (65/71) and 45.1% (32/71) in group I, which were significantly higher than those in group II (36.7 and 14.2%, 140/381 and 54/381, respectively, P < 0.01). A total of 21 patients (4.6%, 21/452) experienced recurrence after undergoing a gastrectomy and hematogenic recurrence was the most frequent type of recurrence (2.0%, 9/452). However, in group I, lymphatic recurrence was most frequently observed (7.0%, 5/71), and it was more frequent than in group II (0.3%, 1/381, P < 0.01). The median intervals between gastrectomy and recurrence were 34.5 and 64.0 months in groups I and II, respectively (P < 0.05). CONCLUSIONS: The submucosal cancer with larger size, lymphatic invasion, and vascular invasion has high risks for lymph node metastasis. Furthermore, a strict follow-up for lymphatic as well as hematogenic recurrence is important for the patients with node positive submucosal cancer, especially within 5 years after operation.

Female↗
PubMed1998

Retrograde cerebral perfusion exceeding 120 minutes in aortic arch reconstruction: a report of two cases.

The time limits for retrograde cerebral perfusion (RCP) during aortic arch reconstruction have yet to be clarified. We herein present two cases with periods of RCP exceeding 120 min during aortic reconstruction; both patients recovered uneventfully with no neurological deficits. These data suggest that RCP, as an adjunct to hypothermic circulatory arrest, may prolong the circulatory arrest time and thus prevent ischemic injury of the brain, even when RCP exceeds 120 min.

Aortic Dissection↗
PubMed1998

Inhibition by diazepam of ketamine-induced hyperlocomotion and dopamine turnover in mice.

PURPOSE: To investigate the effects of the benzodiazepine diazepam on ketamine-induced hyperlocomotion and dopamine turnover. METHODS: Adult male ddY mice were used (n = 218). Locomotor activity was measured with four circular activity cages equipped with three photocell sensor units. Interruptions by a mover of the infrared light Peams were recorded on electromechanical counters, and automatically printed every 10 min for three hours after the ketamine injection. All drugs were administered intraperitoneally (i.p.). The concentrations of dopamine and its metabolites in discrete brain regions were measured by high performance liquid chromatography with electrochemical detection. RESULTS: Ketamine (30 mg.kg-1) increased total locomotor activity counts for three hours to 442% of control in mice (P = 0.0001). Diazepam, 3 and 10 mg.kg-1, inhibited, in a dose-dependent fashion, this ketamine-induced hyperlocomotion by 26% (P = 0.0111) and 59% (P = 0.0001), respectively. Regional brain dopamine assays revealed that ketamine (30 mg.kg-1) increased the homovanillic acid:dopamine ratio (one indicator of dopamine turnover) to 121% of control in the nucleus accumbens (P = 0.0065) and to 111% in the striatum (P = 0.0135) at peak locomotion. Diazepam, 3 and 10 mg.kg-1, returned this increase in dopamine turnover produced by ketamine to control levels both in the nucleus accumbens (P = 0.0061 and P = 0.0117, respectively) and in the striatum (P = 0.0004 and P = 0.0047, respectively). CONCLUSION: These results suggest that the inhibition by diazepam of ketamine-induced hyperlocomotion may be related to its ability to suppress the activation of dopamine neurons in the nucleus accumbens and striatum.

Anesthetics, Intravenous↗
PubMed1998

[A successful conversion of failed fontan circulation to total cavopulmonary connection in a case of tricuspid atresia without pulmonary stenosis].

A 12-year-old boy was first admitted to Tokyo Metropolitan Children's Hospital at 2 days of age with the diagnosis of tricuspid atresia without pulmonary stenosis, normally related great arteries, ventricular septal defect, and persistent left superior vena cava (PLSVC). He underwent pulmonary artery banding at the age of 1 year and atrial septectomy at 2.9 years. At the age of 6.3 years, he underwent successful Bjork operation in conjunction with closure of a trial and ventricular septal defects. Late after surgery, however, he developed progressive intolerance to exercise (NYHA III), cardiomegaly, and depressed ST segments in the left precordial leads. Catheter examination at the age of 11.9 years disclosed moderately elevated pressures (15 mmHg) in the right atrium and pulmonary artery, depressed left ventricular function with ejection fraction (EF) of 0.48, and marked dilatation of the coronary sinus (CS). Right atriography revealed retrograde filling of the dilated CS up to the junction with PLSVC. With supposition that the combined elevation of the volume and pressure loads on CS had disturbed both coronary circulation and ventricular function, he, at the age of 12 years, underwent take down of the Fontan circulation and conversion to the total cavopulmonary connection (TCPC). His postoperative recovery was uneventful and, at 2.5 years after the latest surgery, he is leading a normal life. The findings of the chest roentgenogram and electrocardiogram reverted to normal and EF returned to the normal value (0.66). This experience draws us to conclude that conversion to TCPC is a safe and effective mean to salvage the patients with failed Fontan circulation. This experience also suggests that dilatation of CS is a predictor of the failed or failing Fontan circulation.

Child↗
PubMed1998

The effect of Y-25510 injection on the serum levels of some cytokines in healthy adult volunteers.

OBJECTIVE: Y-25510 was administered by means of an intravenous drip infusion to healthy adult male volunteers at a dose of 40, 80 or 160 mg in a single-dose study, and at a dose of 160 mg once a day for 7 days in a multiple-dose study. RESULTS: Serum levels of interleukin (IL)-1beta, IL-6 and IL-10 were significantly increased, but there was no change in leukocyte and platelet counts. The peak serum concentration of IL-1beta was nearly maximum at the single doses of 40 and 80 mg, and at the multiple dose of 160 mg per day. The peak serum concentration of IL-6 increased in a dose-dependent manner at a dose of 40 mg or more. For the multiple-dose study, the serum level of IL-10, which remained unchanged in the placebo group, began to increase in the Y-25510 group following the maximum serum level of IL-1beta and IL-6. There were no clinically relevant differences in body temperature and blood pressure after the administration of Y-25510. CONCLUSION: These findings that leukocyte and platelet counts never increased, despite the increment of the IL-1beta and IL-6 production after the administration of Y-25510, may be explained in part by the negative feedback mechanism induced by IL-10.

Adjuvants, Immunologic↗
PubMed1998

Imaging features of subcutaneous sarcoidosis.

OBJECTIVE: This report describes subcutaneous sarcoidosis, focusing on the radiological and magnetic resonance (MR) features of the disease. DESIGN AND PATIENTS: The cases of four patients (one male and three female, age range 36-75 years) who had subcutaneous sarcoidosis with no other organs affected were reviewed. Lesions were nodular in two cases, and in the other two were diffuse. RESULTS: Computed tomography (CT) demonstrated a well-defined, homogeneous, and enhanced lesion in the nodular cases. However, in the diffuse cases, CT showed a heterogeneous, honeycomb-like appearance and little enhancement. Angiography showed a fine stain in the arterial phase. MR imaging of the nodular lesions was homogeneous with a signal intensity similar to muscle on T1-weighted images but heterogeneous with a higher signal than muscle on T2-weighted images. Diffuse lesions showed a striped or mesh pattern with intermediate signal intensity on both T1- and T2-weighted images. Contrast-enhanced MR images showed slight enhancement. CONCLUSIONS: Subcutaneous sarcoidosis should be considered in the differential diagnosis when a patient presents with the radiological and MR features described.

Adult↗