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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 19 recordsLinked to original sources
PubMed2006

Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes.

AIMS/HYPOTHESIS: Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown. MATERIALS AND METHODS: We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT. RESULTS: Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-alpha or peroxisome proliferator-activated receptor-gamma, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-gamma coactivator-1alpha or nuclear respiratory factor 1. CONCLUSIONS/INTERPRETATION: Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes.

Aged↗
PubMed2006

Comparative study on osteoconductivity by synthetic octacalcium phosphate and sintered hydroxyapatite in rabbit bone marrow.

Octacalcium phosphate (OCP) is thought to be a precursor of the mineral crystals in biological apatite. Synthetic OCP has been shown to be converted into an apatite structure when implanted in murine calvarial bone, to enhance bone regeneration more than synthetic hydroxyapatite (HA), and to degrade faster than biodegradable beta-tricalcium phosphate. This study was designed to investigate whether OCP implantation enhances the formation and resorption of new bone (remodeling) concomitant with OCP degradation when implanted intramedullary in a rabbit femur for 12 weeks, compared to sintered HA ceramic. Histological and histomorphometric analyses using undecalcified specimens showed that the area of bone apposition was significantly higher on OCP than on HA between 2 and 3 weeks, whereas it subsequently became smaller on OCP than on HA. The area attacked by multinucleated giant cells, including tartrate-resistant acid phosphatase (TRAP)-positive cells, was significantly higher for OCP than for HA at 8 weeks. Radiography revealed resorption of OCP but not of HA. The results disclose some osteoconductive characteristics of synthetic OCP in the bone marrow space: (1) enhancement of bone regeneration at the initial bone apposition stage and (2) stimulation of resorption of the newly formed bone coupled with OCP biodegradation mediated by TRAP-positive osteoclast-like cells. These results suggest that synthetic OCP would be a more useful bone substitute than HA in implant applications where rapid bone formation and concomitant implant resorption are important considerations.

Acid Phosphatase↗
PubMed2005

Bandwidth analysis of solvation dynamics in a simple liquid mixture.

The time-dependent energy distribution of solvation dynamics is studied by molecular dynamics simulations of a Lennard-Jones mixture. We calculate the response functions of the average and the variance which correspond to the spectral peak shift and bandwidth. Our calculation shows that the variance relaxation is slower than that of the average. The result agrees qualitatively with the experimental results. Dividing the obtained response functions into subcomponents caused by each solvent, we find that the relaxation is dominated by that solvent which strongly interacts with the solute. Extracting the redistribution component from the response functions, we find that it causes the slower relaxation of the response function. Thus, we conclude that the difference of the slower relaxations between the average and variance is caused by the redistribution process.

Journal Article↗
PubMed2005

Critical period for activity-dependent elimination of corticospinal synapses in vitro.

There is no in vitro model of the critical periods for developmental plasticity, the time windows of plastic changes during development, which may hinder in-depth mechanistic analysis. We have shown previously that the corticospinal tract with synaptic connections can be reconstructed in in vitro co-cultures using slices of the sensorimotor cortex and spinal cord of the rat. In our in vitro system, corticospinal synapses form widely over spinal gray matter during early development, after which those on the ventral side are eliminated in an activity and N-methyl-D-aspartate (NMDA)-dependent manner. A detailed quantitative analysis of the time course of sensitivity to an NMDA blocker was made with this system. Synapse distribution was evaluated by recording field excitatory post-synaptic potentials evoked by deep cortical layer stimulation. Corticospinal axon terminal distribution was examined by anterograde labeling with biocytin. We showed that the D-2-amino-5-phosphonovaleric acid (APV) effect is irreversible for at least the length of culture. When APV was removed from the medium before 6 days in vitro(DIV) or after 11 DIV, elimination of ventral synapses was not blocked. APV sensitivity showed a clearly defined time window. A 6-11 DIV application was necessary and sufficient for the full, irreversible block of synapse elimination. From 6-11 DIV, APV sensitivity seems to decrease gradually but not linearly. This system provides an in vitro model of critical periods for developmental plasticity of central synapses which up to now has not been available.

2-Amino-5-phosphonovalerate↗
PubMed2004

Optical selection rules in light emission from the scanning tunneling microscope.

It is reported that optical selection rules still apply in light emission from the scanning tunneling microscope (STM). Linear polarization of isochromat light emitted from the tunneling gap between a STM tip made of tungsten (W) and a silicon (Si) sample with a (001) clean surface strongly depends on the bias voltage between tip and sample. The results show that pi* and sigma* surface states, for example, of the Si(001) sample contribute to emission of p- and s-polarized light, respectively, in accordance with optical selection rules.

Journal Article↗
PubMed2004

Genes for systemic vascular complications are differentially expressed in the livers of type 2 diabetic patients.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes. METHODS: Liver biopsy samples were obtained from twelve patients with Type 2 diabetes and from nine non-diabetic patients. To assay gene expression globally in the livers of both groups, we made complementary DNA (cDNA) microarrays consisting of 1080 human cDNAs. Relative expression ratios of individual genes were obtained by comparing cyanine 5-labelled cDNA from the patients with cyanine 3-labelled cDNA from reference RNA from the liver of a non-diabetic patient. RESULTS: On assessing the similarities of differentially expressed genes, the gene expression profiles of the twelve diabetic patients formed a separate cluster from those of the non-diabetic patients. Of the 1080 genes assayed, 105 (9.7%) were up-regulated and 134 (12%) were down-regulated in the diabetic livers (p<0.005). The genes up-regulated in the diabetic patients included those encoding angiogenic factors such as vascular endothelial growth factor, endothelin and platelet-derived growth factor. They also included TGF superfamily genes such as TGFA and TGFB1 as well as bone morphogenetic proteins. Among the down-regulated genes in the diabetic patients were molecules defending against stress, e.g. flavin-containing monooxygenase and superoxide dismutase. CONCLUSIONS/INTERPRETATION: These findings suggest that livers of patients with Type 2 diabetes have gene expression profiles indicative of an increased risk of systemic vascular complications.

Adult↗
PubMed2004

Safety and efficacy of epidural cooling for regional spinal cord hypothermia during thoracoabdominal aneurysm repair.

Twenty-four consecutive patients underwent epidural cooling as an adjunct to elective thoracoabdominal aortic repair under moderate systemic hypothermia. One patient suffered from postoperative paraplegia (4%), and another died from subarachnoidal hemorrhage (4%). Details of the technique, the associated care, and the pitfalls will be discussed.

Aortic Aneurysm, Abdominal↗
PubMed2004

[Spinal cord protection during most or all of descending thoracic or thoracoabdominal aneurysm repair].

OBJECTIVES: The purpose of this study is to evaluate usefulness of perfusion cooling for regional spinal cord hypothermia during most or all of thoracic or thoracoabdominal aneurysm repair. METHODS: From 1987 to 2003, 103 patients underwent most or all of thoracic or thoracoabdominal aneurysm repair. Forty-eight patients underwent operation using distal aortic perfusion, mild hypothermia and segment sequential repair (group MH). Fifty-five patients underwent the same operation as group MH except epidural perfusion cooling and drainage of cerebrospinal fluid (CSF) [group EC & CSFD]. The aorta was replaced sequentially in segment and several paris of intercostal and lumbar arteries were reconstructed in 2 groups. RESULTS: Cardiopulmonary bypass time of group MH and group EC & CSFD was averaged 235 and 241 minutes, respectively. The lowest CSF temperature in group EC & CSFD was averaged 24.7 degrees C, and the difference between nasopharyngeal and CSF temperature was averaged 6.4 degrees C. The rate of spinal cord injury of group MH and EC & CSFD was 10.4% and 3.6%, respectively. Hospital mortality of group MH and EC & CSFD was 8.3% and 5.5%, respectively. The incidence of spinal cord injury and hospital mortality of group EC & CSFD were decreased compared to them of group MH. CONCLUSION: We conclude that the perfusion cooling of epidural space and CSF drainage are effective method in reducing postoperative spinal cord injury.

Adult↗
PubMed2003

Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren's syndrome. IV immunoglobulin.

Ataxic sensory neuronopathy with Sjögren's syndrome is a devastating neurologic complication for which there is no established treatment. IV immunoglobulin (IVIG) was given to five patients with severe disabilities for an average of 12 years. Four patients showed remarkable improvement, two of whom responded after the first course. The authors conclude that IVIG is safe and effective to treat even chronically debilitated patients who have the disease, presumably because it ameliorates smoldering inflammation.

Aged↗
PubMed2003

Neurotoxicity of an endogenous brain amine, 1-benzyl-1,2,3,4-tetrahydroisoquinoline, in organotypic slice co-culture of mesencephalon and striatum.

Organotypic slice co-culture of the ventromedial portion of the mesencephalon and striatum was used to evaluate the neurotoxicity of 1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous brain amine related to Parkinson's disease. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline is specifically increased in the cerebrospinal fluid of patients with Parkinson's disease and induces parkinsonian features in the monkey and mouse. Here, it decreased the dopamine content of the cultured mesencephalon in both dose- (10-100 microM) and time- (24 h to 7 days) dependent manners. This result suggests that the neurotoxicity of 1-benzyl-1,2,3,4-tetrahydroisoquinoline is correlated with the overall exposure (concentration multiplied by exposure time). Culture with 100 microM 1-benzyl-1,2,3,4-tetrahydroisoquinoline for 24 h irreversibly reduced the dopamine content. Furthermore, culture with 100 microM 1-benzyl-1,2,3,4-tetrahydroisoquinoline for 10 days caused morphological changes, including cell body shrinkage and distortion of dendritic morphology, in tyrosine hydroxylase-positive cells in the mesencephalon and reduced the number of cells by half. The increase in lactate dehydrogenase activity in the media produced by 1-benzyl-1,2,3,4-tetrahydroisoquinoline was significant in culture of the mesencephalon alone or its co-culture with striatum, but not in cultures of other brain regions. We suggest that 1-benzyl-1,2,3,4-tetrahydroisoquinoline is toxic to tyrosine hydroxylase-positive cells in the ventral mesencephalon and that it is correlated with the integral of the concentration by time of exposure. Thus a low concentration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline may first induce a decrease in the dopamine content then shrinkage of the cell body, followed by the slow death of dopaminergic neurons over a long period. This is the first report that indicates 1-benzyl-1,2,3,4-tetrahydroisoquinoline exerts neurotoxicity at the cellular level, and reveals in part the character of its neurotoxicity.

Animals↗
PubMed2002

In vitro formation of corticospinal synapses in an organotypic slice co-culture.

In order to study biological properties of the corticospinal tract, we have reconstructed this system in an in vitro slice culture preparation. Motor cortex and spinal cord slices, prepared from newborn rats, were co-cultured on pored membranes for 16-24 days. Anterograde labeling with biocytin showed that substantial neural connections had formed between the cortex and spinal cord slices. Retrograde labeling with horseradish peroxidase or 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate demonstrated that the parent cells were located primarily in the deeper layer of the cortex, as is found in vivo. Stimulation of the deep layer of the cortex elicited extracellular postsynaptic responses and intracellular excitatory postsynaptic potentials (EPSPs) in the co-cultured spinal cord that were mediated by the 1-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/ kainate-type glutamate receptor. The intracellular injection of biocytin after EPSPs were recorded showed that one-third of these cells were large stellate cells, which are thought to be motoneurons, while a large portion of the remaining labeled cells were bipolar cells of smaller sizes. Using this reconstructed in vitro preparation, we recorded field EPSPs (fEPSPs) along a 100-microm-interval lattice in the spinal gray matter, which allowed the quantitative evaluation of synapse formation. The fEPSP amplitudes were more than two-fold larger when the forelimb cortex was co-cultured with cervical cord rather than lumbar cord. However, hindlimb cortex did not show this preference. The fEPSP amplitudes were more than twice as large when the dorsal side of the spinal cord was adjacent to the cortex than the ventral side. In summary, we have reconstructed the corticospinal projection and synapses in vitro using cortical and spinal explants. This system allows for an efficient quantitative evaluation of synapse formation and for studies of postsynaptic cells. Our results suggest that synapse formation shows preferences along and perpendicular to the neuraxis of the spinal cord.

Animals↗
PubMed2002

[Long-term results of total aortic arch replacement using selective cerebral perfusion].

From June 1994 to July 2001, 92 consecutive patients underwent total aortic arch replacement using hypothermic selective cerebral perfusion. Forty-four patients had nondissecting fusiform or saccular aneurysms (non-ruptured 34, ruptured 10), and 48 patients had dissection (acute 37, chronic 11). Hospital mortality rate was 6.8% in the nondissecting group and 6.3% in the dissecting group. No major operative cerebral complications were observed. There were 9 late deaths in the nondissecting group and 5 late deaths in the dissecting group. The actuarial survival rate was 61.6% after 100 months in the nondissecting group and 82.5% after 86 months in the dissecting group (p = 0.5128). In the postoperative aortic accidents, there were 2 cases of the descending aortic rupture and 2 cases of cholesterol crystal embolization in the nondissecting group and 3 cases of thoracoabdominal grafting, 2 cases of re-operation in the ascending aorta and 1 case of descending aortic rupture in the dissection group. The actuarial freedom from aortic accidents was 88% after 100 months in the nondissecting group and 80% after 86 months in the dissecting group (p = 0.6908). Our surgical outcome of total aortic arch replacement using hypothermic selective cerebral perfusion are satisfactory.

Aged↗
PubMed2001

Changes of oligosaccharides and fatty acids in monkey hippocampus by synaptic potentiation.

We measured the release of free fatty acids and structural changes of glycoprotein glycans induced by tetraethylammonium (TEA) salt in hippocampal slices of cynomolgus monkey brain. The release of free fatty acids in the hippocampal slices occurred after synaptic potentiation by TEA in a different manner from rat hippocampus. Arachidonic acid release in monkey hippocampus occurred much faster than that in rat. Several types of glycans of monkey hippocampal glycoproteins were determined depending on the duration time after TEA treatment. 5-Mannose was increased within 2 min, while polysialoglycans were increased after 5 min or later. Comparative study of glycans of monkey and rat hippocampal slices revealed the presence of relatively larger amount of sialo- and multi-anntenary glycans in rat than in monkey. These results indicate that the depolarizing stimulation of monkey hippocampal slices induced the change of glycoprotein glycan structures and release of free fatty acids in a different manner from rat hippocampus.

Animals↗
PubMed2001

A pivotal role of Rho GTPase in the regulation of morphology and function of dendritic cells.

Dendritic cell (DC) is the most potent activator of CD4+ T cells and has unique dendrites and veils. To explore the function of Rho in DC, exoenzyme C3 from Clostridium botulinum was used as a specific inhibitor of Rho. Treatment of DC with C3 (DC/C3) resulted in profound morphological changes by losing dendrites and emerging of shrunk membrane processes that were in parallel with marked reduction of polymerized actin in the marginal area. Inactivation of Rho-associated coiled coil-containing kinase (p160ROCK) by a specific ROCK inhibitor Y-27632 also led to disappearance of dendrites of DC with retaining large membrane expansions. In scanning electron microscopy, untreated DCs interacted with CD4+ T cells more efficiently than DC/C3. Conjugate formation assay showed that the number of DCs associated with CD4+ T cells was 2-fold higher in untreated DCs than that of DC/C3. Alloantigen-presenting capacity of DC/C3 was significantly suppressed in a dose-dependent manner. Because C3 treatment did not affect the surface expression of HLA, costimulatory, and adhesion molecules of DC, we examined cytokine production of DC and naive CD4+ T cells to further elucidate the inhibitory mechanism of MLR. Unexpectedly, DC/C3 increased IL-12 production after LPS stimulation. Naive CD4+ T cells cocultured with DC/C3 produced the increased percentage of IFN-gamma-producing cells, whereas the percentage of IL-2-producing T cells was decreased. These results demonstrate that Rho GTPase in DC controls both characteristic shape and immunogenic capacity.

ADP Ribose Transferases↗
PubMed2001

Infrared spectroscopic study on the properties of the anhydrous form II of trehalose. Implications for the functional mechanism of trehalose as a biostabilizer.

FTIR spectra were obtained for several different states of trehalose including dihydrate crystal, anhydrous form II (designated by Gil, A. M.; Belton, P. S.; Felix V. Spectrochim. Acta 1996, A52, 1649-1659), anhydrate crystal, dried melt, amorphous solid and aqueous solution. From the observation of the symmetric and antisymmetric stretch vibrations of the glycosidic linkage, it is found that this sugar assumes at least three types of backbone conformations. Among them, the conformation with C(2) symmetry is characterized as 'open state', which means that the sugar easily absorbs water molecules. The conformation of the sugars in anhydrous form II and in freeze-dried trehalose is shown to be in the open state. Next, the hygroscopic properties of the anhydrate, form II and the amorphous solid are compared based on their IR spectra. Interestingly, form II alone is converted to the original dihydrate in a week under mild environmental-like conditions: relative humidity of 40% and room temperature. These results suggest the possibility that form II plays a role in avoiding the devitrification of the sugar glass. Finally, we discuss the role of form II in preserving freeze-dried biomaterials.

Animals↗