Biomedical subjects
Publications and source records attributed to K Fukuda.
A case of dorsal fracture-dislocation of the proximal interphalangeal joint in which the volar plate had been pulled from its distal attachment without bony or cartilaginous attachments and the lip of the volar plate had also been detached separately and was obstructing full flexion of the joint is presented. A tentative mechanism of causation of this unusual variant of a common injury is suggested.
AIM: To investigate the involvement of interleukin (IL)10 and transforming growth factor (TGF) beta in the development of experimentally induced allergic conjunctivitis in mice. METHODS: Balb/c mice were actively sensitised with ragweed in alum, and then challenged with ragweed in eye drops after 10 days. 24 h later, the conjunctivas, spleens and blood were collected for histological and cytokine expression analyses, proliferation and cytokine production assays and measurement of immunoglobulin (Ig) levels. Mice developing experimentally induced allergic conjunctivitis were injected intraperitoneally with 200 microg of anti-IL10 or anti-TGF beta antibodies at 0, 2, 4, 6 and 8 days (induction phase treatment) or 500 microg of antibodies 2 h before ragweed challenge (effector phase treatment). Normal rat IgG was used for control injections. RESULTS: Treatment with either anti-IL10 or anti-TGF beta antibodies during the induction phase did not affect eosinophil infiltration into the conjunctiva. By contrast, treatment with either antibody during the effector phase suppressed infiltration. During the effector phase, treatment with anti-TGF beta antibody, but not the anti-IL10 antibody, markedly up regulated proliferation and Th2 cytokine production by splenocytes. IL1alpha levels in the conjunctiva were reduced after treatment with either antibody; in addition, eotaxin and tumour necrosis factor alpha levels were reduced after treatment with antibody to TGF beta. CONCLUSIONS: IL10 and TGF beta do not have immunosuppressive roles in the development of experimentally induced allergic conjunctivitis. Rather, they augment the infiltration of eosinophils into the conjunctiva during the effector phase of experimentally induced allergic conjunctivitis.
Using a voltage-imaging technique, we analyzed the acute effect of ischemia, hypoxia and hypoglycemia on the neuronal network function of the rat spinal cord. Ischemic, hypoxic, or hypoglycemic stress was loaded to spinal cord slices with an oxygen- and glucose-free, oxygen-free, or glucose-free mock cerebrospinal fluid, respectively. Depolarizing signals in the dorsal horn, induced by dorsal root stimulation, consisted of fast (pre-synaptic) and slow (post-synaptic) components. The slow component was attenuated much more than the fast component under an ischemic condition (P<0.0002). Post-synaptic neuronal activities in lamina III-IV were suppressed earlier than those in lamina I-II. The nerve fiber was relatively resistant to ischemia. As long as the fast component was preserved in the dorsal horn, the suppression of the fast and slow components was reversible. There was a significant difference (P<0.05) in the recovered slow component sizes between the group in which the fast component was suppressed by more than 20% by ischemia and the group in which the suppression was less than 20%. Further prolonged stress irreversibly eliminated most of the slow component, and attenuated the fast component (to 59+/-8%) accompanied by cellular damage in histology. Suppression of neural activity by hypoxic or hypoglycemic stress was less prominent than that by ischemia. Prolonged ischemic stress suddenly and irreversibly eliminated depolarizing signals in the ventral horn accompanied by morphological damage of motoneurons. Immunohistochemical staining was negative for apoptosis. We have, for the first time, analyzed the processes of spinal cord disturbance induced by ischemia, hypoxia and hypoglycemia at the neuronal network level by directly observing the regional neuronal network activities within the spinal cord. We conclude that synaptic transmission in the dorsal horn, especially in deep regions, is vulnerable and first affected by these stresses. Severe ischemic stress induces irreversible dysfunction of neurons accompanied by eventual cell death in both dorsal and ventral horns.
BACKGROUND: beta-Adrenergic blocking agents may interact with anaesthetics, and several studies suggest that beta-blockers attenuate electroencephalographic responses during general anaesthesia. We have investigated the influence of landiolol, an ultra-short-acting beta 1-adrenoceptor antagonist, on the electroencephalographic effect of isoflurane in pigs. METHODS: Ten swine were anaesthetized through inhalation of 2% isoflurane. The inhalational concentration was then decreased to 0.5% and maintained for 25 min, before being returned to 2% and maintained for a further 25 min (control period). After control measurements, infusion of landiolol (at 0.125 mg kg(-1) min(-1) for 1 min, and then at 0.04 mg kg(-1) min(-1)) was started. After a 20 min stabilization period, the inhalational concentration was varied as in the control period (40 gamma landiolol). Finally, infusion of landiolol was increased from 0.04 to 0.2 mg kg(-1) min(-1), and after a 20 min stabilization period, the inhalational concentration was again varied as in the control period (200 gamma landiolol). End-tidal isoflurane concentrations and spectral edge frequencies were recorded throughout the study. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequency vs effect-site concentration. RESULTS: There were no significant differences in the effect of isoflurane among the conditions used. Landiolol did not shift the concentration-effect relationship [the effect-site concentration that produced 50% of the maximal effect was 1.35 (0.17)% under control conditions, 1.30 (0.12)% at 40 gamma landiolol, and 1.38 (0.30)% at 200 gamma landiolol]. CONCLUSION: Landiolol does not alter the electroencephalographic effect of isoflurane.
OBJECTIVE: Articular cartilage is an avascular tissue in which chondrocytes are exposed to hypoxic conditions. We previously demonstrated that reactive oxygen species (ROS) induced apoptosis of chondrocytes. We also demonstrated that nitric oxide (NO) was induced when chondrocytes were exposed to hypoxia and that NO inhibited the ROS-induced apoptosis. Hyaluronan (HA) is a high molecular weight glycosaminoglycan whose antioxidative effects have been reported. The purpose of the present study was to determine whether HA synthesis was induced in chondrocytes exposed to hypoxia, and, if so, whether the hypoxia-induced HA synthesis is regulated by NO. METHODS: Bovine articular chondrocytes were used in this study. Levels of HA were determined by the sandwich enzyme-binding assay. Expression of HA synthase (HAS) was determined with reverse transcription-polymerase chain reaction. The production of NO was examined using the Griess reaction. We also determined inducible nitric oxide synthase (iNOS) enzyme synthesis using the histochemistry and Western blot analysis. RESULTS: Chondrocytes cultured under hypoxic conditions exhibited enhanced HA synthesis. When the NO inhibitors, L-NMMA and L-NAME, were added, the hypoxia-enhanced HA levels in the culture medium were significantly inhibited. CONCLUSIONS: Endogenous NO synthesis plays an important role in hypoxia-enhanced HA synthesis.
This study characterised the population structure of Legionella pneumophila by comparing the rpoB (300-bp) and dotA (360-bp) sequences of 267 isolates (18 reference strains, 149 Korean isolates and 100 Japanese isolates). In addition to the six clonal subgroups established previously, four subgroups, P-V to P-VIII, were identified. Subgroupings based on rpoB and dotA sequences were found to correlate with the source of the isolates, and this data may be useful for future epidemiological studies. Fourteen (five Korean and nine Japanese) isolates showed incongruent subgroupings in the rpoB and dotA trees, suggesting that genetic exchange among subgroups, and even among subspecies, may occur frequently in nature.
It is known that the excessive generation of reactive oxygen species (ROS) is a significant factor in tissue injury observed in many disease states. To determine whether extreme levels of mechanical stress applied to osteoblasts enhances ROS synthesis, we loaded cyclic tensile stretch on osteoblast-like HT-3 cells. Cyclic tensile stretch loaded on these cells clearly enhanced ROS synthesis in a time- and magnitude-dependent fashion. Cyclic tensile stretch also enhanced superoxide dismutase (SOD) activity. The disruption of microfilaments with cytochalasin D abolished the stress-induced ROS synthesis. Rotenone, an inhibitor of the mitochondrial electron transport chain, enhanced stress-induced ROS synthesis. These data suggest that actin filament and mitochondria are involved in this action.
Our previous studies suggest that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer. This study was conducted to determine whether alteration of RUNX3 gene expression could be detected in the normal-looking gastric remnant mucosa, and to ascertain any difference in the potential of gastric carcinogenesis between the anastomotic site and other areas in the remnant stomach after distal gastrectomy for peptic ulcer (RB group) or gastric cancer (RM group), by analysing RUNX3 expression with special reference to topography. A total of 89 patients underwent distal gastrectomy for gastric cancer from the intact stomach (GCI group) and 58 patients underwent resection of the remnant stomach for gastric cancer (RB group: 34 cases, RM group: 24 cases). We detected RUNX3 and gene promoter methylation by in situ hybridisation, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and methylation-specific PCR. The interval between the initial surgery and surgery for remnant gastric cancer (interval time) was 10.4 years in the RM group, and 27.5 years in the RB group. Cancers in the RB group were significantly more predominant in the anastomosis area (P<0.05). Within the tumour, downregulation of RUNX3 expression ranged from 74.7 to 85.7% in the three groups. The rate of downregulation of RUNX3 of adjacent mucosa was 39.2% (11 in 28 cases) in RB and 47.6% (10 in 21 cases) in RM, which are significantly higher than that of the GCI group (19.5%, 17 in 87 cases). In noncancerous mucosa of the remnant stomach in the RB group, RUNX3 expression decreased more near the anastomosis area. In the RM group, however, there were no significant differences in RUNX3 expression by sampling location. Based on RUNX3 downregulation and clinical features, residual stomach mucosa of the RM group would have a higher potential of gastric carcinogenesis compared to the RB or GCI group. Gastric stump mucosa of the RB group has higher potential especially than other areas of residual stomach mucosa. Measurement of RUNX3 expression and detection of RUNX3 methylation in remnant gastric mucosa may estimate the forward risk of carcinogenesis in the remnant stomach.
Panic disorder (PD) is a complex condition that is further complicated by its numerous inducers, which include hypercapnia, hypoxia, sodium lactate, caffeine and cholecystokinin. It seems unlikely that there are specific suffocation receptors for each of these inducers in the brain. The pulmonary neuroepithelial bodies (NEBs), which are situated at the bifurcation point of the small bronchi, act as storage cells for 5-hydroxytryptamine (5-HT) and sensors for suffocation. If we suppose that PD might represent an inflammation of the NEBs, bradykinin (BK) which augments the airway hyper-response to diverse indcers might cause these cells to release 5-HT along with peptides and panneuroendcrine markers from their dence-core secretory granules. It was revealed that BK with 5-HT could cross the blood-brain barrier (BBB). When 5-HT released from these cells along with BK cross the BBB, the release of 5-HT at the axonal terminals in the serotonergic neurons in the brain will be inhibited, since the 5-HT1 autoreceptor have a higher affinity for 5-HT than do the 5-HT2 receptors. The inhibition of 5-HT at the axonal terminal causes to suppress the periaqueductal gray matter, which inhibits flight reactions to impending danger, pain or asphyxia. In short, this serotonergic situation might bring about PD. According to this theory, the type of inducer that the PD patient is exposed to is unimportant as long as it stimulates the NEBs, and through the effect of 5-HT and BK, PD would be revaluated as a somatic disease that directly and reversibly affects the brain.
Accurate identification of aspermic Fasciola forms in Japan remains difficult because of their morphological variations. In order to characterize the forms genetically, nucleotide sequences of ribosomal internal transcribed spacer (ITS1 and ITS2) and mitochondrial cytochrome c oxidase I (COI) and NADH dehydrogenase I (NDI) genes in 34 liver flukes from 16 prefectures in Japan were analysed. Two major forms represented by Fsp 1 and Fsp 2 had sequences identical to or closely resembling those of F. hepatica and F. gigantica, respectively, in all the 4 DNA markers and were mainly distributed in northern and eastern-western parts of Japan, respectively. Fsp 1 and Fsp 2 would have been introduced into Japan with infected cattle of 2 distinct lineages via the Korean Peninsula and spread through limited parts of Japan (northern and eastern-western parts) together with the movement of each cattle lineage. The Japanese form (Fsp 1/2), which showed heterozygosity in ribosomal DNA and Fsp 2 haplotype in mitochondrial DNA, may have originated in interspecific cross hybridization between paternal F. hepatica and maternal F. gigantica.
Bullous pemphigoid (BP) is associated with autoantibodies to the 180-kDa BP antigen (BP180), and the antigenic site exists on noncollagenous 16a (NC16a) domain of BP180. We now report a male BP patient whose IgG autoantibodies did not react against the NC16a domain of BP180 by either immunoblotting or ELISA, whereas they did react with BP180 extracted from normal human keratinocytes. Anti-BP180 cicatricial pemphigoid was ruled out due to the lack of conjunctival mucosal involvement and the absence of scarring in the oral cavity. Our findings indicate that there is an antigenic reactive region other than NC16a on the extracellular domain of BP180. There have been few reports describing detailed clinical features of BP caused by autoantibodies targeting antigenic sites other than the NC16a domain. We conclude that it is difficult to differentiate their clinical features from those associated with autoantibodies targeting the NC16a domain of BP180.
We evaluated the effectiveness of intentional hypercapnia against hypotension after induction of anaesthesia with thiopental and isoflurane (TI) or propofol (P). For each group, 24 patients were anaesthetized with thiopental 4 mg kg(-1) (TI) or propofol 2 mg kg(-1) (P) for tracheal intubation and then lightly anaesthetized with isoflurane at 0.6% end-expiratory concentration (TI) or by 6 mg kg(-1) h(-1) infusion of propofol (P). In both anaesthesia groups, patients were randomly assigned to either normocapnia (end-tidal CO(2) = 35 mmHg) or hypercapnia (end-tidal CO(2) = 45 mmHg), which were achieved through adjusting the tidal volume. Systolic arterial pressure (SAP) 15 min after intubation was compared with the preanaesthetic baseline value. Under normocapnia, both TI and P induced a comparable, statistically significant suppression of SAP by approximately 20 mmHg from baseline. Hypercapnia prevented the decrease in SAP in TI but not in P. No patient in the TI-hypercapnia group experienced SAP below 100 mmHg, unlike those in the other groups. In conclusion, mild hypercapnia was effective in the prevention of hypotension in patients receiving thiopental followed by 0.6% end-expiratory isoflurane, but not in patients receiving 6 mg kg(-1) h(-1) propofol.
BACKGROUND: Nociceptin is the endogenous agonist of the opioid receptor-like (ORL) 1 receptor (NOP), and both nociceptin and NOP are widely expressed in the brain and spinal cord, which are target organs of general anaesthetics. As nociceptin has been reported to be involved in modulating pain mechanisms and stress responses, it is possible that the activity of the nociceptin system affects the anaesthetic potency of general anaesthetics. To address this possibility, we investigated the minimum alveolar concentrations (MACs) of various volatile anaesthetics in nociceptin receptor knockout mice (NOP-/-) and wild-type mice (NOP+/+). METHODS: We used male NOP-/- mice and NOP+/+ mice. MACs for halothane, isoflurane and sevoflurane were determined by the tail-clamp method. RESULTS: MACs for halothane, isoflurane and sevoflurane in NOP-/- mice were 1.60 (SD 0.06), 1.68 (0.08) and 3.36 (0.07)%, respectively. In NOP+/+ mice, MACs for halothane, isoflurane and sevoflurane were 1.59 (SD 0.07), 1.72 (0.07) and 3.38 (0.09)%, respectively. CONCLUSION: MACs in NOP-/- mice did not significantly differ from those in NOP+/+ mice for halothane, isoflurane and sevoflurane. This result suggests that the nociceptin system does not affect the anaesthetic potency of volatile anaesthetics.
To elucidate the pathogenesis of carcinomas in the extrahepatic bile duct, we investigated the histomorphological characteristics of adenomas and early carcinomas induced in the extrahepatic bile duct of hamsters. Syrian hamsters underwent a cholecystoduodenostomy along with a dissection of the common duct, while also being administered N-nitrosobis(2-oxopropyl)amine (BOP). The tumors that arose from the extrahepatic bile duct included 10 adenomas and 55 early carcinomas in 56 of the 156 hamsters sacrificed. All the adenomas were found to be polypoid in shape. The early carcinomas, which were restricted within the mucosal layer of the bile duct, showed the following three different growth patterns: (1) protruding type in 41 (75%), consisting of 27 polypoid and 14 papillary tumors; (2) superficial spreading type in 9 (16%); and (3) periductal glandular type in 5 (9%). There were no depressed tumors observed. Carcinomas existing either alone or associated with adenomas were evident in 12 (22%) tumors, and 11 of these were polypoid. Atypical papillary hyperplasia within the tumor mass was noted in 22 early carcinomas (40%) and was particularly prominent in papillary type tumors. These results support the concept of an adenoma-carcinoma sequence in the majority of polypoid tumors of the extrahepatic bile duct. Atypical papillary hyperplasia might also be premalignant, and these precursor lesions should reflect the growth patterns of tumors, at least in the early stage of tumorigenesis.
Radiation therapy is a powerful tool for the treatment of oesophageal cancer. We established radioresistant cell lines by applying fractionated irradiation in order to identify differentially expressed genes between parent and radioresistant cells. Six oesophageal cancer cell lines (TE-2, TE-5, TE-9, TE-13, KYSE170, and KYSE180) were treated with continuous 2 Gy fractionated irradiation (total dose 60 Gy). We compared expression profiles of each parent and radioresistant lines on a cDNA microarray consisting of 21168 genes. In the fractionated irradiation trial, four radioresistant sublines (TE-2R, TE-9R, TE-13R, KYSE170R) were established successfully, and we identified 19 upregulated and 28 downregulated genes common to radioresistant sublines. Upregulated genes were associated with apoptosis and inflammatory response (BIRC2 and COX-2), DNA metabolism (CD73), and cell growth (PLAU). Downregulated genes were associated with apoptosis (CASP6), cell adhesion (CDH1 and CDH3), transcription (MLL3), and cell cycle (CDK6). Some of these genes were known to be associated with radiation response, such as COX-2, but others were novel. Reverse transcription-polymerase chain reaction confirmed that genes selected by cDNA microarray were overexpressed in clinical specimens of radioresistant cases. Global gene analysis of radioresistant sublines may provide new insight into mechanisms of radioresistance and effective radiation therapy.
Textures, textural transformation, and formation and annihilation of a single vortex were investigated in narrow cylinders with 100 microm radius in A-phase under rotation up to 6.28 rad/sec. Three textures were found, depending on the cooling conditions of the sample through the superfluid transition temperature T(c). We found the gyromagnetic effect of textures; that is, two textures (A or B) could be selected either by applying a magnetic field in parallel or anti-parallel to the rotation axis. The critical angular speed of a single vortex formation Omega(f) and that of annihilation Omega(a) for each texture were measured. The textural transformation in type A texture was induced by rotation. Both type A and B textures held macroscopic angular momentum along the rotation axis. We identified the texture for type A, B, and C as Mermin-Ho, radial disgyration, and a soliton type of defect along the axis, respectively.
OBJECTIVE: Because articular cartilage has no vascular supply, chondrocytes are hypoxic under normal physiological conditions. Nitric oxide (NO) plays an important role in chondrocyte damage, such as apoptosis. Although oxygen stress with hydrogen peroxide was found to cause chondrocyte damage, these data were obtained under normoxic (21% O2) conditions. We investigated the effects of hypoxia on hydrogen peroxide-induced chondrocyte damage METHODS: Bovine articular chondrocytes were used in this study. Proteoglycan (PG) synthesis and the induction of apoptosis were analyzed with [(35)S]-sulfate incorporation and annexin V staining, respectively. The induction of NO was examined using a fluorescent probe and RT-PCR. RESULTS: Cells maintained at 5% O2 had the maximum PG synthesis. Under normoxic conditions, hydrogen peroxide inhibited PG synthesis and induced annexin V positive cells in a dose-dependent fashion. However, in those cells cultured under hypoxic (5%) conditions, the hydrogen peroxide-induced annexin V expression was attenuated. Chondrocytes exposed to hypoxia showed induction of NO. When the hypoxia-induced NO was inhibited, the hypoxia-enhanced PG synthesis was abolished and hydrogen peroxide clearly induced cell damage. CONCLUSIONS: Endogenous NO induced by hypoxia protects chondrocytes from apoptosis induced by an oxidative stress.
OBJECTIVE: Mechanical stress is an essential factor in the pathogenesis of osteoarthrosis. We sought to determine whether the strain-mediated alteration in proteoglycan (PG) synthesis was modulated by nitric oxide (NO) synthesis. METHODS: Cyclic tensile strain was applied to bovine articular chondrocytes. PG and NO synthesis were determined by [35S] sulfate incorporation and chemiluminescence analysis, respectively. To determine the expression of inducible NO synthase (iNOS), quantitative RT-PCR was used. RESULTS: Enhanced PG and NO synthesis were evident when cyclic tensile strain was applied to chondrocytes seeded on fibronectin-coated plates. When NO production was inhibited, PG synthesis was further enhanced. CONCLUSIONS: Cyclic tensile strain loaded on the chondrocytes enhanced NO synthesis and this enhanced NO inhibited PG synthesis.