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Biomedical subjects

D Ito

Publications and source records attributed to D Ito.

At least 19 recordsLinked to original sources

Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy.

STUDY DESIGN: Review. OBJECTIVES: To highlight the value of investigating the effects of putative therapeutic interventions in clinical spinal cord injury (SCI) in domestic dogs. SETTING: England, UK. METHODS: Many experimental interventions in laboratory rodents have been shown to ameliorate the functional deficits caused by SCI; the challenge now is to determine whether they can be translated into useful clinical techniques. Important differences between clinical SCI in human patients and that in laboratory rodents are in the size of the spinal cord and heterogeneity of injury severity. A further key issue is whether the statistical difference in outcome in the laboratory will translate into a useful difference in clinical outcome. Here, we stress the value of investigating the effects of putative therapies in clinical SCI in domestic dogs. The causes of injury, ability to categorise the severity and methods available to measure outcome are very similar between canine and human patients. Furthermore, postmortem tissue more rapidly becomes available from dogs because of their short lifespan than from human patients. RESULTS: The role that investigation of canine SCI might play is illustrated by our preliminary trials on intraspinal transplantation of olfactory glial cells for severe SCI. CONCLUSIONS: This canine translational model provides a means of 'filtering' putative treatments before human application.

Animals↗

FFT analysis of the X-ray tube voltage waveforms of high-frequency generators for radiographic systems.

PURPOSE: To present a novel method for analyzing the voltage waveform from high-frequency X-ray generators for radiographic systems. MATERIAL AND METHODS: The output signal of the actual voltage across the tube of a high-frequency generator was measured using the built-in voltage sense taps that are used for voltage regulation feedback in X-ray generators. The output signal was stored in an analyzing recorder, and the waveforms were analyzed using FFT analysis. The FFT analysis of high-frequency generators consisted of obtaining the power spectrum, comparing the major frequency components in the tube voltage waveforms, and examining the intensity of each frequency component. RESULTS: FFT analysis enables an objective comparison of the complex tube voltage waveforms in high-frequency X-ray generators. FFT analysis detected the change in the X-ray tube voltage waveform that occurred when there were problems with the high-frequency generator. CONCLUSION: High-frequency X-ray generators are becoming the universal choice for radiographic systems. The X-ray tube voltage and its waveform are important features of an X-ray generator, and quality assurance (QA) is important, too. As a tool for engineers involved in the design and development of X-ray generators, we can see that our methods (FFT analysis) might have some value as a means of describing generator performance under varying conditions. Furthermore, since the X-ray tube voltage waveform of a high-frequency generator is complex, FFT analysis may be useful for QA of the waveform.

Algorithms↗

Hand-assisted laparoscopic resection of serous cystadenoma of the pancreas.

It is difficult to exclude the possibility of malignancy of pancreatic cystic tumors because a biopsy of the pancreas is hard to obtain. The indication of open surgery for those cystic tumors without evidence of malignancy is controversial. Therefore, laparoscopic or laparoscopically assisted procedure would be an adequate choice of treatment for cystic tumors of the pancreas. Hand-assisted laparoscopic distal pancreatectomy with preservation of the spleen and the splenic artery and vein was performed for two cases of pancreatic cystic tumors. Three ports and one hand port were used. After careful dissection and accurate hemostasis between the pancreas and splenic vessels, laparoscopic distal pancreatectomy was carried out using an endoscopic linear stapler. There were no perioperative complications. The pathological diagnoses were oligocystic serous cystadenoma and solitary cystic serous cystadenoma, respectively. Hand-assisted, spleen-preserving laparoscopic distal pancreatectomy with preservation of the splenic artery and vein is a feasible procedure for the treatment of benign or borderline-malignant cystic lesions of the distal pancreas.

Adult↗

Automated guidance algorithms for a space station-based crew escape vehicle.

An escape vehicle was designed to provide an emergency evacuation for crew members living on a space station. For maximum escape capability, the escape vehicle needs to have the ability to safely evacuate a station in a contingency scenario such as an uncontrolled (e.g., tumbling) station. This emergency escape sequence will typically be divided into three events: The first separation event (SEP1), the navigation reconstruction event, and the second separation event (SEP2). SEP1 is responsible for taking the spacecraft from its docking port to a distance greater than the maximum radius of the rotating station. The navigation reconstruction event takes place prior to the SEP2 event and establishes the orbital state to within the tolerance limits necessary for SEP2. The SEP2 event calculates and performs an avoidance burn to prevent station recontact during the next several orbits. This paper presents the tools and results for the whole separation sequence with an emphasis on the two separation events. The first challenge includes collision avoidance during the escape sequence while the station is in an uncontrolled rotational state, with rotation rates of up to 2 degrees per second. The task of avoiding a collision may require the use of the Vehicle's de-orbit propulsion system for maximum thrust and minimum dwell time within the vicinity of the station vicinity. The thrust of the propulsion system is in a single direction, and can be controlled only by the attitude of the spacecraft. Escape algorithms based on a look-up table or analytical guidance can be implemented since the rotation rate and the angular momentum vector can be sensed onboard and a-priori knowledge of the position and relative orientation are available. In addition, crew intervention has been provided for in the event of unforeseen obstacles in the escape path. The purpose of the SEP2 burn is to avoid re-contact with the station over an extended period of time. Performing this maneuver requires knowledge of the orbital state, which is obtained during the navigation state reconstruction event. Since the direction of the delta-v of the SEP1 maneuver is a random variable with respect to the Local Vertical Local Horizontal (LVLH) coordinate system, calculating the required SEP2 burn is a challenge. This problem was solved using elements of neural network theory for model-free function approximation and decision making.

Algorithms↗

Inhibitor of cyclooxygenase-2 induces cell-cycle arrest in the epithelial cancer cell line via up-regulation of cyclin dependent kinase inhibitor p21.

Cyclooxygenase-2 is the rate-limiting enzyme in synthesis of prostaglandins and other eicosanoids. Prior reports have shown that inhibition of cyclooxygenase-2 activity, either by selective inhibitors or by antisense oligonucleotide, results in suppression of growth of squamous cell carcinoma cell lines which express high cyclooxygenase-2 levels, such as NA, a cell line established from a squamous cell carcinoma of the tongue. To investigate the mechanisms by which cyclooxygenase-2 inhibitors suppressed growth of these cells, the effects of NS-398, the selective cyclooxygenase-2 inhibitor, on cell-cycle distribution were examined. NS-398 induced G0/G1 cell-cycle arrest in NA cells which expressed cyclooxygenase-2. G0/G1 arrest induced by NS-398 was accompanied by up-regulation of cyclin-dependent kinase inhibitor p21, but not by up-regulation of the other cyclin-dependent kinase inhibitors. Transfection with p21 antisense oligonucleotide inhibited cell-cycle arrest induced by NS-398. Accumulation in G0/G1 was also observed in NA cells transfected with cyclooxygenase-2 antisense oligonucleotide. On the other hand, NS-398-treated NA cells showed a loss of plasma membrane asymmetry, a marker of early events in apoptosis. However, NS-398 did not induce other morphological and biochemical changes related to apoptotic cell death. These results suggest that cyclooxygenase-2 inhibitor induces G0/G1 cell-cycle arrest in NA cells by up-regulation of p21. Our results also suggest that NS-398 is not sufficient to complete the whole process of apoptosis in NA cells, although it induces an early event in apoptosis.

Apoptosis↗

Sequencing-based typing of HLA-B*51 alleles and the significant association of HLA-B*5101 and -B*5108 with Behçet's disease in Greek patients.

Behçet's disease (BD) is widely known to be strongly associated with human leukocyte antigen (HLA) B51 in many different ethnic groups.Recently, HLA-B51 allele typing of Greek BD patients was performed to study the distribution of B*5101-B*5107 alleles in this Greek population, the B51 antigen strongly associated with BD was found to be predominantly encoded by allele B*5101. As it is now known that the B51 antigen can be encoded by 21 alleles, B*5101-B*5121, we performed HLA-B*51 allele genotyping among 58 Greek patients with BD. After serological HLA typing, typing of HLA-B*51 alleles was performed using the polymerase chain reaction-sequencing-based typing (PCR-SBT) method. The frequency of the B51 antigen was found to be significantly higher in the patient group as compared with the control group (75.9% of patients vs 22.0% of controls. In the genotyping of B51 alleles, 34 out of 44 B51-positive patients possessed B*5101, 13 out of the 44 carried B*5108. In contrast, all of the 9 B51-positive normal controls carried B*5101. This study revealed a strong association between Greeks with BD, both B*5101, B*5108, provided important insights into the molecular mechanism underlying the association between HLA status, this disease.

Alleles↗

Notch3 gene polymorphism and ischaemic cerebrovascular disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a type of hereditary stroke and dementia. More than 90% of patients with CADASIL have mutations in the Notch3 gene. All mutations either create or destroy a cysteine residue in the epidermal growth factor-like repeats. In addition, five polymorphisms, which lead to amino acid substitutions, have been identified within the Notch3 coding sequence. However, whether these polymorphisms affect Notch signalling or are involved in cerebrovascular diseases is unknown. In the present study, we investigated a possible association between a T6746C polymorphism in the Notch3 coding region and the occurrence of symptomatic ischaemic cerebrovascular disease (CVD) was investigated. Two hundred and thirty five patients with CVD, as confirmed by brain CT or MRI, and 315 age and sex matched control subjects were analyzed for genotype frequencies of the T6746C polymorphism in Notch3. The genotype distributions were: patients with CVD, C/C 14.0%, C/T 45.5%, and T/T 40.4%; controls, C/C, 14.3%; C/T, 47.9%; T/T, 37.8%. The Japanese population has a higher C allele frequency of the T6746C polymorphism than European populations. There was no significant difference between the T6746C polymorphism in patients with CVD and controls (chi(2)=0.414, p=0.813). This was confirmed by the results of multiple logistic regression analysis including established risk factors (chi(2) =4.65, p=0.311). In conclusion, the results indicate that T6746C polymorphism in the intracellular domain of the Notch3 gene is not associated with an increased risk for CVD.

Aged↗

Up-regulation of the Ire1-mediated signaling molecule, Bip, in ischemic rat brain.

The endoplasmic reticulum (ER) is thought to play important roles in various neurological diseases via multifactorial and complex mechanisms. The Ire1-mediated signal is part of one ER signaling pathways; the signal induces the expression of an ER-resident protein, Bip/GRP78, and is thought to be involved in cell death under ER stress. In this study, we examined time-dependent Bip expression after transient middle cerebral artery occlusion and characterized the Bip-positive cells. Ire1- mediated molecules, Bip, were rapidly up-regulated in the ischemic area after 3.5 h recirculation. Their immunoreactivity continued to increase until 24-48 h. Immunofluorescence staining revealed Bip up-regulation in ischemic neurons, which were TUNEL positive. Our studies suggest that the Ire1-mediated signal might be associated with ischemic neuronal damage.

Animals↗

Activation of NG2-positive oligodendrocyte progenitor cells during post-ischemic reperfusion in the rat brain.

This study examines the alteration of oligodendrocyte progenitor cells which express membrane NG2 chondroitin sulfate proteoglycan after focal ischemia in the rat brain. Adult male Sprague-Dawley rats were subjected to 90 min occlusion of the middle cerebral artery, followed by reperfusion time of up to 2 weeks. The distribution and morphological changes in NG2-positive oligodendrocyte progenitor cells were immunohistochemically examined. Stellate-shaped NG2-positive cells with multiple branched processes were detected in both the gray and white matter of normal brain. After 2 weeks of reperfusion, NG2-positive cells in the area surrounding the infarction site (peri-infarct area) clearly showed enlarged cell bodies with hypertrophied processes. These stained strongly for NG2. Although the number of NG2-positive cells was increased significantly in the peri-infarct area, it decreased markedly in the infarct core compared to controls. Double immunostaining revealed that these NG2-positive cells were neither astrocytes nor microglia, but NG2-positive oligodendrocyte progenitor cells. These progenitor cells are known to differentiate into oligodendrocytes. As such, this upregulation of NG2 expression may be an adaptive mechanism attempting to remyelinate rat brain tissue after ischemic insult. Only further study will elucidate this hypothesis.

Animals↗

Craniofacial abnormalities in Japanese patients with severe obstructive sleep apnoea syndrome.

OBJECTIVE: To clarify that factors besides obesity play an important role in the development of obstructive sleep apnoea syndrome (OSAS) in Japanese patients, we compared craniofacial structures in patients with severe OSAS with those of normal controls. METHODOLOGY: The craniofacial structures of 60 Japanese patients with severe OSAS and 30 normal controls were evaluated using standard cephalometric analysis. Patients were stratified according to body mass index (BMI): non-obese, BMI < 25; moderately obese, BMI = 25-30, severely obese, BMI > 30. RESULTS: The SNA (sella to nasion to subspinale angle) was significantly smaller in the patient groups than in the controls. The SNB (sella to nasion to supramentale angle) and NSBa (cranial base flexure) were significantly smaller in the non-obese and moderately obese patients than in controls. The MP-H (distance from the mandibular plane to the hyoid bone) and the PNS-P (distance from the posterior nasal spine to the tip of the soft palate) were significantly longer in the patient groups than in the controls. The PNS-P was significantly longer in the severely obese patients than in the non-obese patients. CONCLUSIONS: Japanese patients with severe OSAS have enlargement of the soft tissues and palate as well as craniofacial bony structural abnormalities. This is particularly apparent in non-obese patients.

Body Mass Index↗

Optimal continuous positive airway pressure in patients with obstructive sleep apnoea: role of craniofacial structure.

Although nasal continuous positive airway pressure (CPAP) is effective in improving nocturnal obstructive apnoea, daytime sleepiness and well-being in patients with obstructive sleep apnoea syndrome (OSAS), not all patients tolerate this treatment. Since optimal CPAP titration is essential to maintain compliance, it is important to elucidate the factors that help to determine the optimal pressure. However, the determinants of the optimal CPAP level are controversial. The subjects comprised 27 Japanese male patients with OSAS who underwent standard polysomnography (PSG), pulmonary function tests, arterial blood gas analysis, cephalometry and CPAP titration. Twenty normal controls also underwent cephalometric analysis. The apnoea-hypopnoea index (AHI), mean oxygen saturation (mean SaO2) and the lowest SaO2 during sleep were found to be 54.7+/-22.6, 89.0+/-5.6%, and 69.7+/-9.0%, respectively by PSG. The mean optimal CPAP was 9.6+/-1.8 cmH2O. The cephalometric angles (SNA, SNB and NSBa) were similar to those found in the control subjects. but MP-H, and PNS-P were significantly longer than those in the control subjects as shown by cephalometry. The optimal CPAP was correlated with the mean SaO2 (P<0.0001), neck circumference (P<0.05) and three cephalometric variables (NSBa: P<0.01, MP-H: P<0.05, PNS-P: P<0.05). Multiple, step-wise, regression analysis showed that the mean SaO2 and NSBa were independent variables that best predicted the optimal CPAP. These variables accounted for 57.5% of the total variance (R2=0.575, P<0.001). Optimal CPAP was closely correlated with oxygen desaturation during sleep. However, the craniofacial structure had additional effects such as an independent factor in determining the optimal CPAP level.

Adult↗

Phosphorylation of cyclic adenosine monophosphate response element binding protein in oligodendrocytes in the corpus callosum after focal cerebral ischemia in the rat.

Phosphorylation of cyclic adenosine monophosphate (AMP) response element binding protein (CREB) was examined immunohistochemically in the corpus callosum of the rat brain at various time points after 90-minute focal cerebral ischemia. Focal ischemia was induced by occlusion of the middle cerebral artery (MCA) using the intraluminal suture method. Sham animals showed that numerous oligodendrocytes (OLGs) constitutively express unphosphorylated CREB. Local cerebral blood flow (lCBF) measured by the 14C-iodoantipyrine method was reduced from 44.2 +/- 15.4 (mL 100 g(-1) min(-1)) to 18.4 +/- 3.8 and from 53.9 +/- 14.4 to 4.8 +/- 4.5 in the medial and the lateral regions of the corpus callosum, respectively, during MCA occlusion (MCAO). After release of the MCAO, lCBF recovered to the control level in each region. The medial region of the corpus callosum showed a marked increase in phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, and it remained increased until 2 weeks of recirculation as it gradually declined. The activation of CREB phosphorylation in the OLGs was accompanied by expression of antiapoptotic protein bcl-2, normal staining with cresyl violet, and negative TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) staining. Myelination detected by immunostaining with anti-myelin basic protein (MBP) antibody and anti-myelin associated glycoprotein (MAG) antibody remained normal in the medial region of the corpus callosum. The lateral region of the corpus callosum showed a significant but only transient increase in phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, which was followed by a rapid decrease during the subsequent recirculation period. Expression of bcl-2 was suppressed in this region, and demyelination became apparent. These findings suggest that signal transduction through CREB phosphorylation may be closely associated with survival of OLGs and maintenance of myelination in the corpus callosum after cerebral ischemia.

Adenomatous Polyposis Coli Protein↗

Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain.

BACKGROUND AND PURPOSE: Iba1 is a novel calcium-binding protein and is specifically expressed in microglia in the brain. It has been suggested that Iba1 plays an important role in regulation of the function of microglia. In the present study we examined time-dependent Iba1 expression after transient middle cerebral artery occlusion and characterized microglial activation in various brain regions. METHODS: Rat middle cerebral artery occlusion was induced by the intraluminal filament technique. After 1.5 hours of transient ischemia, Iba1 expression was examined by immunohistochemical and immunoblot analyses. The microglial activation in association with ischemic severity was characterized by double immunostaining with other specific markers. RESULTS: In the peri-ischemic area, heavily Iba1 immunoreactive cells rapidly appeared at 3.5 hours after reperfusion. Immunoreactivity was further increased and peaked at 7 days. In the ischemic core, round Iba1-positive cells, which may be blood-borne monocytes, appeared from 24 hours and reached a peak at 4 to 7 days. Double immunostaining revealed that activated microglia in the peri-ischemic area upregulated Iba1 expression but were negative for the macrophage marker ED1. ED1-positive cells were clearly restricted to the ischemic core. CONCLUSIONS: These findings suggest the following: (1) Iba1 expression may be associated with microglial activation in ischemic brain, and Iba1 immunostaining can be useful to evaluate the pathophysiological roles of activated microglia in ischemic injury. (2) Expression of ED1 antigen is strictly restricted to severe ischemic damage, whereas activated microglia in the peri-ischemic area showed Iba1 upregulation without ED1. Therefore, microglia may exhibit difference of antigenicity in the severity of ischemic brain injury.

Animals↗

Mitochondrial DNA polymorphism of a triploid form of Fasciola in Japan.

Mitochondrial DNA polymorphism was characterized in a triploid form of Fasciola found in Japan in comparison with F. hepatica, F. gigantica and Korean Fasciola worm. Seventy worms of Fasciola from Japan, three of F. hepatica from Uruguay and Australia, two of F. gigantica from Thailand and one of Fasciola from Korea were used in the study. Mitochondrial DNA polymorphism was detected by restriction fragment length polymorphism (RFLP) using eight restriction enzymes, BamH I, Bgl II, Dra I, EcoR I, EcoR V, Hind III, Mfl I and Sca I. Three different types (types 1, 2 and 3) were detected from 76 Fasciola worms used in the study. Eight of 70 Japanese worms were categorized in type 2 (F. gigantica type), and the remaining 62 were in type 3 (F. hepatica type).

Animals↗

[Targets of treatment in the acute phase of cerebral infarction].

In the acute phase of cerebral infarction, many experimental data suggest that free radicals including superoxide, hydroxy radical and nitric oxide are one of the most important factors to cause brain damage. We have clearly detected nitrotyrosine (a marker of endogenous production of peroxynitrite, which is readily produced from superoxide and nitric oxide) in neurons and intraparenchymal vascular walls during post-ischemic reperfusion. Free radical scavengers thus seem to be very promising tools of treatment, and one of them (edaravone) has recently been approved for clinical use in Japan. CREB (cyclic AMP response element binding protein) is a DNA-binding transcription factor, and its function is activated by phosphorylation of Ser133 residue. CREB plays important roles in neuronal development, synaptic plasticity and regeneration. We have found that phosphorylation of CREB is significantly and persistently increased in surviving neurons and oligodendrocytes in post-ischemic brain, while this phosphorylation is only transiently increased in neurons and oligodendrocytes which eventually die. These data suggest that CREB phosphorylation plays an important role in protection of ischemic brain tissue. Oligodendrocyte progenitor cells (OPC) remain abundant throughout the adult brain, and retain their ability to become not only mature oligodendrocytes, but also neurons. We have recently found that OPC are significantly activated and proliferate in the peri-infarct area at 1-2 weeks after ischemia, suggesting that OPC may be involved in the repair mechanisms of ischemic brain. Future targets of stroke treatment should include enhancement of intrinsic protection mechanisms such as CREB phosphorylation and activation of progenitors cells.

Acute-Phase Reaction↗

Induction of CTL responses by simultaneous administration of liposomal peptide vaccine with anti-CD40 and anti-CTLA-4 mAb.

Activation of APC via CD40-CD40 ligand pathway induces up-regulation of costimulatory molecules such as B7 and production of IL-12. Interaction between B7 on APC and CD28 on naive T cells is necessary for priming the T cells. On the other hand, interaction between B7 on APC and CTLA-4 on activated T cells transduces a negative regulatory signal to the activated T cells. In the present study, we attempted to generate tumor-specific CTL by s.c. administration of antigenic peptides encapsulated in multilamellar liposomes (liposomal peptide vaccine) with anti-CD40 mAb and/or anti-CTLA-4 mAb. Liposomal OVA257-264 and anti-CD40 mAb or anti-CTLA-4 mAb were administrated to C57BL/6 mice and the splenocytes were cocultured with OVA257-264 for 4 days. The splenic CD8+ T cells showed a significant cytotoxicity against EL4 cells transfected with cDNA of OVA. In addition, administration of both anti-CD40 and anti-CTLA-4 mAb enhanced the CTL responses. Considerable CTL responses were induced in MHC class II deficient mice by the same procedure. This finding indicated that CTL responses could be generated even in the absence of Th cells. When BALB/c mice were immunized with pRL1a peptide that are tumor-associated Ag of RLmale symbol1 leukemia cells using the same procedure, significant CTL responses were induced and prolonged survival of the BALB/c mice was observed following RLmale symbol1 inoculation. These results demonstrate that anti-CD40 mAb and anti-CTLA-4 mAb function as immunomodulators and may be applicable to specific cancer immunotherapy with antitumor peptide vaccine.

Abatacept↗