Metabolic disorders related to obesity and periodontal disease.
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Adipocytes↗
Biomedical subjects
Toshiyuki Saito
Publications and source records attributed to Toshiyuki Saito.
Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Actinobacillus actinomycetemcomitans.
Previous epidemiologic studies have suggested that periodontal disease is closely related to obesity and glucose tolerance. As the level of adiponectin, an adipocyte-derived cytokine, in plasma had been reported to decrease in obese and type 2 diabetes patients, we explored the role of adiponectin in the etiology of periodontitis using the D clone of RAW264, a clone that exhibits highly efficient osteoclast formation, to determine whether adiponectin acts as a regulatory molecule in osteoclast formation stimulated by lipopolysaccharide of periodontopathic bacteria. We observed that adiponectin acted as a potent inhibitor of osteoclast formation stimulated by Toll-like receptor 4 (TLR4) ligand and receptor activator of NF-kappaB ligand (RANKL). Because NF-kappaB is an important transcription factor in osteoclast formation, we examined the effect of adiponectin on its transcriptional activity. A luciferase assay showed that adiponectin was able to inhibit the TLR4-mediated NF-kappaB activity in RAW264 cells. In addition, we observed that the cytokine was actually able to inhibit TLR4-mediated expression of the gene for inducible nitric oxide synthase and production of nitric oxide in the cells. These observations strongly suggest that adiponectin may function as a negative regulator of lipopolysaccharide/RANKL-mediated osteoclast formation in periodontal disease.
Actinobacillus Infections↗
T-type Ca2+ channels contribute to IBMX/forskolin- and K(+)-induced Ca(2+) transients in porcine olfactory receptor neurons.
T-type Ca(2+) channels are low-voltage-activated Ca(2+) channels that control Ca(2+) entry in excitable cells during small depolarization above resting potentials. Using Ca(2+) imaging with a laser scanning confocal microscope we investigated the involvement of T-type Ca(2+) channels in IBMX/forskolin- and sparingly elevated extracellular K(+)-induced Ca(2+) transients in freshly isolated porcine olfactory receptor neurons (ORNs). In the presence of mibefradil (10microM) or Ni(2+) (100microM), the selective T-type Ca(2+) channel inhibitors, IBMX/forskolin-induced Ca(2+) transients in the soma were either strongly (>60%) inhibited or abolished completely. However, the Ca(2+) transients in the knob were only partially (<60%) inhibited. Ca(2+) transients induced by 30mM K(+) were also partially ( approximately 60%) inhibited at both the knob and soma. Furthermore, ORNs responded to as little as a 2.5mM increase in the extracellular K(+) concentration (7.5mM K(+)), and such responses were completely inhibited by mibefradil or Ni(2+). These results reveal functional expression of T-type Ca(2+) channels in porcine ORNs, and suggest a role for these channels in the spread Ca(2+) transients from the knob to the soma during activation of the cAMP cascade following odorant binding to G-protein-coupled receptors on the cilia/knob of ORNs.
1-Methyl-3-isobutylxanthine↗
More than 40,000 transcripts, including novel and noncoding transcripts, in mouse embryonic stem cells.
To study the transcriptome of embryonic stem cells, we used a new gene expression profiling method that can measure the expression levels of unknown and rarely expressed transcripts precisely. We detected a total of 33,136 signal peaks representing transcripts in mouse embryonic stem cells, E14. Subsequent random cloning of the peaks suggests that mouse embryonic stem cells express at least 40,000 transcripts, of which about 2,000 are still unknown. In addition, we identified 1,022 noncoding transcripts, several of which change depending on differentiation in gene expression. Our database provides a high-resolution expression profile of E14 cells and is applicable to other mouse embryonic stem cell analyses. It includes most transcription regulation factor-encoding genes and a significant number of unknown and noncoding transcripts.
Animals↗
Intensity of odorant stimulation affects mode of Ca2+ dynamics in rat olfactory receptor neurons.
We investigated the relation between the intensity of odorant stimulation and the mode of spatiotemporal Ca(2+) dynamics in Fluo-4-loaded rat olfactory receptor neurons (ORNs) using a confocal laser scanning microscope. We found that relatively smaller Ca(2+) transients remained confined to the knob while larger ones spread to the soma with latency. Prolonged odor exposure ensured the spread of Ca(2+) transients from the knob to the soma. Upon exposing ORNs to progressively increasing concentrations of odor, the Ca(2+) transients that were confined to the knob at lower concentrations extended to the soma at higher concentrations. Stimulation with progressively increasing concentrations of forskolin plus IBMX yielded identical results. Partial inhibition of adenylyl cyclase by MDL12330A changed the odor response extending to the soma to a response confined to the knob. Blocking of L-type Ca(2+) channels by nifedipine reduced the magnitude of the response extending to the soma but had no effect on the response confined to the knob. It is thus suggested that Ca(2+) transients confined to the knob represent weak stimulation, and, speculatively, such responses either constitute inhibitory responses or indicate weak excitatory responses that fail to outstand the spontaneous electrical noise of ORNs.
Aniline Compounds↗
The medial branch of the lateral branch of the posterior ramus of the spinal nerve.
UNLABELLED: In the needle insertion of epidural anesthesia with the paramedian approach, the needle can pass through the longissimus muscle in the dorsum of the patients. When the needle touches a nerve in the muscles, the patients may experience pain in the back. Obviously, the needle should avoid the nerve tract. To provide better anesthetic service, analysis of the structure and where the concerned nerves lie in that region is inevitable. MATERIAL AND METHOD: We studied five cadavers in this study. Two cadavers were fixed with Thiel's method. With these cadavers, we studied the nerve running of the posterior rami of the spinal nerve from the nerve root to the distal portion. Three of them were used for the study of transparent specimen, with which we studied the course and size of the nerve inside the longissimus muscle. RESULTS: We observed there were three branches at the stem of the posterior rami of the spinal nerves between the body segment T3 and L5, i.e. medial branch, medial branch of the lateral branch and lateral branch of the lateral branch. The medial branch of the lateral branch supplied to the longissimus muscle. With the transparent specimen, we found that there were different nerve layouts between the upper thoracic, lower thoracic, upper lumbar, and lower lumbar segments in the medial branch of the lateral branch in the longissimus muscle. In the lower thoracic and upper lumbar segments, the medial branch of the lateral branch of the upper lumbar segments produced layers nerve network in the longissimus muscle. L1 and L2 nerves were large in size in the muscle. CONCLUSION: In the upper lumbar segments the medial branch of the lateral branch of the posterior rami of the spinal nerve produced dense network in the longissimus muscle, where the epidural needle has high possibility to touch the nerve. Anesthetists have to consider the existence of the medial branch of the lateral branch of the posterior rami of the spinal nerve when they insert the needle in the paramedical approach to the spinal column.
Cadaver↗
DNA damage-dependent cell cycle checkpoints and genomic stability.
In response to genotoxic stress, which can be caused by environmental or endogenous genotoxic insults such as ionizing or ultraviolet radiation, various chemicals and reactive cellular metabolites, cell cycle checkpoints which slow down or arrest cell cycle progression can be activated, allowing the cell to repair or prevent the transmission of damaged or incompletely replicated chromosomes. Checkpoint machineries can also initiate pathways leading to apoptosis and the removal of a damaged cell from a tissue. The balance between cell cycle arrest and damage repair on one hand and the initiation of cell death, on the other hand, could determine if cellular or DNA damage is compatible with cell survival or requires cell elimination by apoptosis. Defects in these processes may lead to hypersensitivity to cellular stress, and susceptibility to DNA damage, genomic defects, and resistance to apoptosis, which characterize cancer cells. In this article, we have noted recent studies of DNA damage-dependent cell cycle checkpoints, which may be significant in preventing genomic instability.
Animals↗
Effect of melatonin injected into the third ventricle on growth hormone secretion in Holstein steers.
The effects of melatonin (MEL) injection into the third ventricle (3V) on growth hormone (GH) secretion were investigated in conscious Holstein steers. A stainless steel cannula was stereotaxically implanted in the 3V based on the ventriculogram. In Exp. 1, three doses of MEL (100, 300 or 600 microg) were injected into the 3V through the cannula and the GH concentration after the injection was determined. In Exp. 2, intracerebroventricular (icv) and intravenous (iv) injections of MEL (100 microg) and GH-releasing hormone (GHRH; 0.25 microg/kg body weight), respectively, were performed simultaneously to examine the effect of MEL on GHRH-induced GH release. The icv injection of MEL significantly stimulated GH release at 100 microg. The increase in GH concentrations by 100 microg of MEL was persistent. Intravenous injection of GHRH dramatically increased GH release. The injection of MEL did not alter GHRH-induced GH release. These results suggest that MEL stimulates GH secretion possibly through the hypothalamus in cattle.
Animals↗
The influence of current and former smoking on gingival bleeding: the Hisayama study.
BACKGROUND: Previous studies have shown that smoking is a risk factor for periodontitis and that it has a suppressive effect on gingival bleeding. This study examined the relationship between smoking, including past smoking, and periodontal conditions, mainly gingival bleeding, in a community-based health investigation. METHODS: Smoking status was examined in 958 subjects, along with the quantity of tobacco currently or previously smoked (never, former light, former heavy, current light, and current heavy). We analyzed the influence of smoking on probing depth (PD), clinical attachment loss (CAL), and gingival bleeding on probing (BOP). RESULTS: In multivariate logistic regression analyses, current heavy smokers were at a significantly greater risk for having a higher proportion of teeth with PD > or =4 mm and a higher proportion of teeth with CAL > or =5 mm; however, they had a lower risk for having a high BOP than did those who had never smoked. Moreover, both former light and former heavy smokers had significantly lower risks for high BOP. When the analysis was limited to subjects with PD > or =4 mm, former heavy and current heavy smokers showed a significant suppression of high BOP compared to never smokers. CONCLUSION: This study suggests that smoking is significantly associated with PD and CAL and that current and past smoking has a suppressive effect on BOP.
Adult↗
Radiation-induced response of micro RNA expression in murine embryonic stem cells.
Despite the importance of embryonic stem cells in embryology and regenerative medicine, their response to DNA damage is not fully understood. Here we studied the expression profiles of small RNAs approximately 22 nucleotides long called micro RNAs, which play an important role in developmental regulation in plants and animals. We identified a group of micro RNAs with increased expression after exposure to radiation (compared with murine fibroblasts) and characterized putative target genes. These micro RNA sequences are conserved in mice, chickens and humans with similar genomic organizations, suggesting that a common regulatory network is involved in stem cell regulation in response to DNA damage. Micro RNAs might be useful as therapeutic tools to control DNA damage response in pluripotent stem cells.
Animals↗
Relationship between periodontitis and hepatic condition in Japanese women.
The liver is an important organ closely associated with lipid and glucose metabolism. This study was performed to clarify the relationship between periodontitis and hepatic condition in apparently healthy Japanese women. A cross-sectional study was performed on 172 apparently healthy, dentulous Japanese women (20-59 years old) who attended a health promotion program at Fukuoka Health Promotion Center. After multivariate adjustment for age, smoking history and oral hygiene, which were known risk factors for periodontitis, the incidence of periodontitis (deepest probing depth > or =4 mm) in females was significantly increased with elevated serum levels of aspartate aminotransferase (AST, p < 0.01), alanine aminotransferase (ALT, p < 0.01) and cholinesterase (p < 0.001), and an AST-to-ALT ratio of less than one (p = 0.02). Further adjustment for either body mass index (BMI) or percent body fat did not attenuate these relationships. These results suggest that hepatic steatosis is associated with periodontitis in Japanese women.
Adult↗
Adiponectin inhibits Toll-like receptor family-induced signaling.
Recent studies have shown that adiponectin, an adipocyte-derived cytokine, acts as a potent inhibitor of inflammatory responses. It has been also demonstrated that bacterial and viral signalings in host cells are triggered via Toll-like receptor (TLR) molecules. Therefore, in the present study, we investigated whether globular adiponectin (gAd) would be able to inhibit TLR-mediated nuclear factor-kappaB (NF-kappaB) signaling in mouse macrophages (RAW264). gAd predominantly bound to the AdipoR1 receptor and suppressed TLR-mediated NF-kappaB signaling. gAd-mediated inhibition of TLR-mediated IkappaB phosphorylation and NF-kappaB activation was eliminated by the pretreatment of cycloheximide. Also their inhibitions of gAd were blocked by preincubation of the cells with an antibody against AdipoR1, but not with an antibody against AdipoR2. Taken together, these findings indicate that adiponectin negatively regulates macrophage-like cell response to TLR ligands via an unknown endogenous product(s).
3T3-L1 Cells↗
Expression of mRNAs for interleukin-4, interleukin-6 and their receptors in porcine corpus luteum during the estrous cycle.
There is increasing evidence that inflammatory cytokines regulate corpus luteum (CL) function in many species. The purpose of the present study was to determine whether interleukin (IL)-4 and IL-6 are expressed in the porcine CL, and whether these cytokines influence porcine luteal steroidogenesis. The gene expressions of IL-4, IL-6 and their specific receptors were determined in the CL of Chinese Meishan pigs during the estrous cycle. Moreover, the effects of these cytokines on progesterone (P(4)), estradiol-17beta (E(2)) and prostaglandin (PG) F2alpha secretion by cultured luteal cells were investigated. IL-4 and IL-6 mRNAs were detected in the CL at all luteal stages. Furthermore, mRNAs of the receptors for IL-4 and IL-6 were clearly expressed in the CL throughout the estrous cycle. Real-time PCR analysis revealed that IL-6 receptor (IL-6R) mRNA expression was higher in the regressed CL (days 19-21 after ovulation) than in the CL at other stages (P<0.01). Exposure of cultured luteal cells obtained from mid-stage CL (days 8-11) to IL-6 (1-100 ng/ml), it inhibited P(4) and E(2) secretion by the cells (P<0.05). Although IL-4 (1-100 ng/ml) did not significantly alter P(4) secretion, it inhibited E(2) secretion by the cells (P<0.05). Neither IL-4 nor IL-6 had any effect on PGF2alpha secretion by the cells. These results suggest that IL-4 and IL-6 are locally produced in the porcine CL, and that they inhibit steroid production from luteal cells via their specific receptors. Collectively, both IL-4 and IL-6 may play roles in regulating porcine CL function throughout the estrous cycle.
Animals↗
Consideration of adult neurogenesis from physiological and patho-physiological aspects.
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Adult↗
Highly conserved linkage homology between birds and turtles: bird and turtle chromosomes are precise counterparts of each other.
The karyotypes of birds, turtles and snakes are characterized by two distinct chromosomal components, macrochromosomes and microchromosomes. This close karyological relationship between birds and reptiles has long been a topic of speculation among cytogeneticists and evolutionary biologists; however, there is scarcely any evidence for orthology at the molecular level. To define the conserved chromosome synteny among humans, chickens and reptiles and the process of genome evolution in the amniotes, we constructed comparative cytogenetic maps of the Chinese soft-shelled turtle (Pelodiscus sinensis) and the Japanese four-striped rat snake (Elaphe quadrivirgata) using cDNA clones of reptile functional genes. Homology between the turtle and chicken chromosomes is highly conserved, with the six largest chromosomes being almost equivalent to each other. On the other hand, homology to chicken chromosomes is lower in the snake than in the turtle. Turtle chromosome 6q and snake chromosome 2p represent conserved synteny with the chicken Z chromosome. These results suggest that the avian and turtle genomes have been well conserved during the evolution of the Arcosauria. The avian and snake sex Z chromosomes were derived from different autosomes in a common ancestor, indicating that the causative genes of sex determination may be different between birds and snakes.
Amino Acid Sequence↗
Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins.
Tight junctions between intestinal epithelial cells prevent ingress of luminal macromolecules and bacteria and protect against inflammation and infection. During stress and inflammation, mast cells mediate increased mucosal permeability by unknown mechanisms. We hypothesized that mast cell tryptase cleaves protease-activated receptor 2 (PAR2) on colonocytes to increase paracellular permeability. Colonocytes expressed PAR2 mRNA and responded to PAR2 agonists with increased [Ca2+]i. Supernatant from degranulated mast cells increased [Ca2+]i in colonocytes, which was prevented by a tryptase inhibitor, and desensitized responses to PAR2 agonist, suggesting PAR2 cleavage. When applied to the basolateral surface of colonocytes, PAR2 agonists and mast cell supernatant decreased transepithelial resistance, increased transepithelial flux of macromolecules, and induced redistribution of tight junction ZO-1 and occludin and perijunctional F-actin. When mast cells were co-cultured with colonocytes, mast cell degranulation increased paracellular permeability of colonocytes. This was prevented by a tryptase inhibitor. We determined the role of ERK1/2 and of beta-arrestins, which recruit ERK1/2 to PAR2 in endosomes and retain ERK1/2 in the cytosol, on PAR2-mediated alterations in permeability. An ERK1/2 inhibitor abolished the effects of PAR2 agonist on permeability and redistribution of F-actin. Down-regulation of beta-arrestins with small interfering RNA inhibited PAR2-induced activation of ERK1/2 and suppressed PAR2-induced changes in permeability. Thus, mast cells signal to colonocytes in a paracrine manner by release of tryptase and activation of PAR2. PAR2 couples to beta-arrestin-dependent activation of ERK1/2, which regulates reorganization of perijunctional F-actin to increase epithelial permeability. These mechanisms may explain the increased epithelial permeability of the intestine during stress and inflammation.
Actins↗
Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis.
We report the identification and characterization of a potent regulator of genomic integrity, mouse and human FRAG1 gene, a conserved homolog of replication factor C large subunit that is homologous to the alternative replication factor C subunits Elg1, Ctf18/Chl12, and Rad24 of budding yeast. FRAG1 was identified in a search for key caretaker genes involved in the regulation of genomic stability under conditions of replicative stress. In response to stress, Atr participates in the down-regulation of FRAG1 expression, leading to the induction of apoptosis through the release of Rad9 from damaged chromatin during the S phase of the cell cycle, allowing Rad9-Bcl2 association and induction of proapoptotic Bax protein. We propose that the Frag1 signal pathway, by linking replication stress surveillance with apoptosis induction, plays a central role in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis.
Amino Acid Sequence↗
Radiotelemetry recording of electroencephalogram in piglets during rest.
A wireless recording system was developed to study the electroencephalogram (EEG) in unrestrained, male Landrace piglets. Under general anesthesia, ball-tipped silver/silver chloride electrodes for EEG recording were implanted onto the dura matter of the parietal and frontal cortex of the piglets. A pair of miniature preamplifiers and transmitters was then mounted on the surface of the skull. To examine whether other bioelectrical activities interfere with the EEG measurements, an electrocardiogram (ECG) or electromyogram (EMG) of the neck was simultaneously recorded with the EEG. Next, wire electrodes for recording movement of the eyelid were implanted with EEG electrodes, and EEG and eyelid movements were simultaneously measured. Power spectral analysis using a Fast Fourier Transformation (FFT) algorithm indicates that EEG was successfully recorded in unrestrained piglets, at rest, during the daytime in the absence of interference from ECG, EMG or eyelid movements. These data indicate the feasibility of using our radiotelemetry system for measurement of EEG under these conditions.
Animals↗