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Biomedical subjects

M Nakata

Publications and source records attributed to M Nakata.

At least 19 recordsLinked to original sources

Aldose reductase inhibition alters nodal Na+ currents and nerve conduction in human diabetics.

BACKGROUND: In diabetic nerves, activation of the polyol pathway via an aldose reductase and the resulting impairment of the Na(+)-K(+) pump would lead to a decreased transaxonal Na+ gradient and thereby reduced nodal Na+ currents. OBJECTIVE: To investigate whether the aldose reductase inhibitor (ARI) epalrestat improves nodal Na+ currents and nerve conduction in human diabetic neuropathy. METHODS: The authors conducted a 6-month, open clinical trial with an ARI, epalrestat, in 30 patients with mild-to-moderate diabetic neuropathy. The latent addition technique and measurements of the strength-duration time constant were used to estimate nodal persistent Na+ currents in median motor axons. Excitability testing and extensive nerve conduction studies including F-wave analyses were performed before and 1 and 6 months after the initiation of treatment with oral epalrestat. RESULTS: Within a month of the start of treatment, there was a significant improvement in nerve conduction, particularly in conduction times across the carpal tunnel and F-wave latencies. The results of latent addition (p < 0.05) and strength-duration time constant (p = 0.06) suggested increased nodal persistent Na+ currents. At 6 months, nerve conduction continued to improve. CONCLUSIONS: Aldose reductase pathway inhibition could rapidly increase nodal Na+ currents and thereby improve the slowing of nerve conduction, presumably because of a restoration of the membranous Na+ gradient.

Adult↗

Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control.

AIMS/HYPOTHESIS: Hyperlipidaemia often occurs in patients with type 2 diabetes mellitus. Though HMG-CoA reductase inhibitors (statins) are widely used for controlling hypercholesterolemia, atorvastatin has also been reported to have an adverse effect on glucose metabolism. Based on these findings, the aim of this study was to investigate the effects of statins on adipocytes, which play pivotal roles in glucose metabolism. METHODS: In 3T3-L1 cells, effects of statins on adipocyte maturation were determined morphologically. Protein and mRNA levels of SLC2A4 and adipocyte marker proteins were determined by immunoblotting and RT-PCR, respectively. Type 2 diabetic NSY mice were treated with atorvastatin for 15 weeks, followed by glucose and insulin tolerance tests and examination of SLC2A4 expression in white adipose tissue (WAT). Seventy-eight Japanese subjects with type 2 diabetes and hypercholesterolaemia were treated with atorvastatin (10 mg/day), and its effects on lipid and glycaemic profiles were measured 12 weeks after treatment initiation. RESULTS: Treatment with atorvastatin inhibited adipocyte maturation, SLC2A4 and C/EBPalpha expressions and insulin action in 3T3-L1 cells. Atorvastatin also attenuated SLC2A4 and C/EBPalpha expressions in differentiated 3T3-L1 adipocytes. These effects were reversed by L. mevalonate or geranylgeranyl pyrophosphate. In NSY mice, atorvastatin accelerated glucose intolerance as a result of insulin resistance and decreased SLC2A4 expression in WAT. In addition to improving hyperlipidaemia, atorvastatin treatment significantly increased HbA(1c) but not fasting glucose levels in diabetic patients, and this effect was greater in the non-obese subgroup. CONCLUSIONS/INTERPRETATION: These results demonstrate that atorvastatin attenuates adipocyte maturation and SLC2A4 expression by inhibiting isoprenoid biosynthesis, and impairs glucose tolerance. These actions of atorvastatin could potentially affect the control of type 2 diabetes.

3T3 Cells↗

Electric-field-induced chirality flipping in smectic liquid crystals: the role of anisotropic viscosity.

We demonstrate the homogeneous and permanent reversal of the chirality of a condensed phase by an applied electric field. Tilted chiral smectic layers exhibit a coupled polarization density and molecular orientation fields which reorient about the layer normal as couple of fixed handedness in response to small applied electric fields. Experiments on some bent-core smectics show that above a threshold field the induced rotation can occur instead about the molecular long axis and that, as a result, the handedness of the phase can be flipped. The effect is quantitatively described by a nonequilibrium dissipative model of chiral smectic dynamics with anisotropic rotational viscosities.

Journal Article↗

Carbohydrate-binding specificities of mouse ficolin A, a splicing variant of ficolin A and ficolin B and their complex formation with MASP-2 and sMAP.

Ficolins are a group of proteins mainly consisting of collagen-like and fibrinogen-like domains and are thought to play a role in innate immunity via their carbohydrate-binding activities. Two types of ficolins have been identified in mice, ficolin A, and ficolin B. However, their structure and function are not fully understood. In this study, we isolated the cDNA encoding a novel variant of ficolin A having a shorter collagen-like domain and a longer gap sequence, which was generated from the ficolin A gene by alternative splicing. We delineated the structure and function of mouse ficolins, including this splicing variant, by preparing the respective recombinants. Recombinant ficolin A, its splicing variant, and ficolin B showed multimeric structures and revealed binding to both N-acetylglucosamine and N-acetylgalactosamine. Interestingly, ficolin B specifically recognized sialic acid residues. Ficolin A and its variant, but not ficolin B, bound to mannose-binding lectin (MBL)-associated serine protease-2 (Masp-2) and small MBL-associated protein (smap), and the resulting complexes showed a potent complement activating capacity. In addition, smap competed with Masp-2 in association with ficolin A and its variant, and inhibited the complement activation by the ficolin A (or ficolin A variant)/MASP-2 complex, indicating its regulatory role in the lectin pathway. These results suggest that ficolin A and its variant function as recognition molecules of the lectin pathway, and ficolin B plays a distinct role through its unique carbohydrate-binding specificity.

Adaptor Proteins, Signal Transducing↗

Thermotropic biaxial nematic liquid crystals.

We have synthesized liquid crystal (LC) mesogens based on a nonlinear oxadiazole unit that exhibit nematic phases near 200 degrees C. Polarized microscopy and conoscopy indicate that these LCs are biaxial nematics. Unambiguous and quantitative evidence for biaxiality is achieved using 2H NMR spectroscopy. "2D powder" spectra, obtained by rotating 2H-labeled samples about an axis perpendicular to the magnetic field at approximately 200 Hz, yield phase biaxiality parameters of approximately 0.1 when coupled with rigorous and proven simulations.

Journal Article↗

Umbilical cord occlusion of the donor versus recipient fetus in twin-twin transfusion syndrome.

OBJECTIVES: To compare the technical characteristics and perinatal outcomes of selected twin-twin transfusion syndrome (TTTS) cases treated with primary umbilical cord occlusion (UCO) of the donor vs. recipient twin. METHODS: TTTS patients who underwent primary UCO via ultrasound endoscopic-guided umbilical cord ligation (UCL) or endoscopic umbilical cord photocoagulation (UCP) were eligible for the study. Primary UCO was offered only if a discordant lethal anomaly was present or by patient choice in TTTS Stages III/IV on the cord of the fetus with abnormal Doppler studies or hydrops. RESULTS: Primary UCO was performed in 25 TTTS cases between July 1997 and June 2002. UCO was performed in six (24%) donor twins and 19 (76%) recipient twins. UCL was performed in 23 cases and UCP in two cases. Overall, 22 (88%) patients had liveborn infants. There were no differences in cotwin survival (100% vs. 84.2%), median gestational age at delivery (34.8 vs. 33.8 weeks) and preterm premature rupture of membranes rate (16.6% vs. 15.7%) whether the donor or recipient twin, respectively, was the subject of UCO. However, two-trocar access (50% vs. 5.3%; P = 0.03) and amnioinfusion (83.3% vs. 0%; P < 0.001) were required more often in the UCO of the donor than of the recipient twin, respectively. Operating time (75 vs. 40 min) was significantly longer in UCO of the donor twin (P = 0.04). UCP was more likely to be used in occlusion of the donor's cord (33%) than of the recipient's cord (0%; P = 0.05). CONCLUSION: Primary UCO of the donor twin is technically more demanding than that of the recipient twin, but perinatal outcomes of the cotwins are comparable.

Chi-Square Distribution↗

Ultrasound assessment of venous blood flow before and after laser therapy: approach to understanding the pathophysiology of twin-twin transfusion syndrome.

OBJECTIVE: To estimate direction and volume of blood exchange between the donor twin and recipient twin by ultrasound assessment of blood flow in the umbilical vein before and after selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS). METHODS: Forty-one TTTS patients underwent Doppler examination of the umbilical vein before and 24 h after SLPCV. The diameter and mean time-averaged velocity of the umbilical vein were estimated. Total umbilical venous flow (TUVF) was calculated as follows: TUVF (mL/min) = mean time-averaged velocity (cm/s) x mean cross-sectional area (cm2) x 60 (s). RESULTS: TUVF was significantly higher in the recipient (111.2 mL/min) than in the donor twin (44.8 mL/min) before SLPCV (P < 0.0001). However, TUVF was no different between the recipient and the donor twin after SLPCV (93.1 vs. 70.7 mL/min, recipient and donor twin, respectively, P = 0.11). The donor twin's TUVF increased after surgery (P < 0.0001), while the recipient twin's TUVF decreased (P = 0.041). The median postoperative increase in the donor twin's TUVF of 25.9 mL/min had a corresponding decrease of TUVF in the recipient twin of 18.1 mL/min (P = 0.27). CONCLUSIONS: Our data suggest that untreated TTTS is characterized by excessive umbilical venous blood flow in the recipient twin relative to the donor twin. Laser surgery results in concordant changes in umbilical venous flow in opposite directions between the donor and recipient twins, eliminating the initial imbalance. Our results lend support to the fundamental hypothesis of unbalanced blood flow exchange (net flow from donor to recipient) between monochorionic twins as the cause for TTTS and that laser surgery eliminates the pathophysiological cause.

Blood Flow Velocity↗

Tri-n-butyltin-induced cytotoxicity on rat thymocytes in presence and absence of serum.

Influence of fetal bovine serum (FBS) on cytotoxicity induced by tri-n-butyltin (TBT), an environmental pollutant, on rat thymocytes was examined to reveal how FBS modifies TBT cytotoxicity. As the medium FBS concentration was increased from 0 to 10%, the cytotoxicity of TBT was dose-dependently reduced when the cells were incubated with 1 microM TBT for 3 h. Almost complete inhibitions of TBT-induced changes in cell viability and population of cells with exposed phosphatidylserine (cells undergoing apoptosis) were observed when the FBS concentration was 10%. Thus, the cytotoxicity induced by 3 h incubation with TBT in FBS-free medium may be different from that in medium containing 10% FBS. However, even in presence of 10% FBS, TBT at concentrations ranging from 10 to 300 nM exerted cytotoxic action on rat thymocytes when the cells were incubated with TBT for 24 h. TBT dose-dependently increased the population of shrunken cells, of which more than 30% were stained with propidium. TBT at 30 nM or more significantly increased the population of cells with hypodiploid DNA, indicating TBT-induced apoptotic cell death. Thus, in the presence of 10% FBS, the prolonged incubation (24 h) of rat thymocytes with TBT at nanomolar concentrations induced apoptosis rather than necrosis.

Animals↗

Periodontal management of an adolescent with Down's syndrome--a case report.

A case of periodontitis in a young adolescent Japanese girl with Down's syndrome is presented in this report. The patient received a monthly preventive course of dental care consisting of mechanical plaque control and oral hygiene instruction. After 2.5 years she recovered from progression of periodontal disease both clinically and microbiologically. The importance of clinical care for periodontitis in Down's syndrome patients is discussed.

Adolescent↗

Characteristics of the gum chewing occlusal phase in children with primary dentition.

Understanding of the growth and development of mandibular function is indispensable to the diagnosis of functional disturbances during childhood. The purpose of this study was to clarify the characteristics of the occlusal phase during gum chewing in children with primary dentition. Chewing motion at the working molar of 14 children with primary dentition and 28 female adults was recorded optoelectrically, and the frontal and sagittal angles of their closing and following opening strokes were measured and compared. In children the closing strokes were entered more vertically and anteriorly than in adults, and the opening strokes shifted to the non-working side in adults but moved to the working side in children. The degree of variance also differed between the two groups; the variance of the frontal angle was larger than that of sagittal angle in adults, but the opposite was true in children. These results suggested that the chewing pattern in children during the occlusal phase is distinctly different from adults and the chewing movement in children is not always less stable than in adults.

Adult↗

Polarization-modulated smectic liquid crystal phases.

Any polar-ordered material with a spatially uniform polarization field is internally frustrated: The symmetry-required local preference for polarization is to be nonuniform, i.e., to be locally bouquet-like or "splayed." However, it is impossible to achieve splay of a preferred sign everywhere in space unless appropriate defects are introduced into the field. Typically, in materials like ferroelectric crystals or liquid crystals, such defects are not thermally stable, so that the local preference is globally frustrated and the polarization field remains uniform. Here, we report a class of fluid polar smectic liquid crystals in which local splay prevails in the form of periodic supermolecular-scale polarization modulation stripes coupled to layer undulation waves. The polar domains are locally chiral, and organized into patterns of alternating handedness and polarity. The fluid-layer undulations enable an extraordinary menagerie of filament and planar structures that identify such phases.

Journal Article↗

Cold-specific and light-stimulated expression of a wheat (Triticum aestivum L.) Cor gene Wcor15 encoding a chloroplast-targeted protein.

Wcor15, a member of the wheat cold-responsive (Cor) gene family, has been isolated and characterized. The deduced polypeptide WCOR15 (MW=14.7 kDa) showed high homology to the previously identified wheat and barley COR proteins. Southern blot analysis using diploid, tetraploid and hexaploid wheat and diploid Aegilops species showed that the wheat and related wild genomes possessed multiple copies of Wcor15 homologues. Five copies were assigned to the homologous group 2 chromosomes by nulli-tetrasomic analysis. Northern blot analysis showed that expression of Wcor15 was specifically induced by low-temperature. Homologous transcripts accumulated in leaves, and light markedly increased their steady-state levels. Bombardment-mediated transient expression analysis of a chimeric CaMV 35S::Wcor15-GFP construct showed protein-targeting to epidermal guard cell chloroplasts in excised spiderwort leaves. A promoter of Wcor15 contained at least three CRT/DRE-like sequence motifs found in Arabidopsis Cor genes and induced the reporter GUS gene expression in leaves of transgenic tobacco plants under low-temperature and light conditions. These results suggest that the functional Cor gene system involving the CRT/DRE cis-element is conserved in both monocotyledonous and dicotyledonous plants.

Amino Acid Sequence↗

Enhanced chirality by adding achiral molecules into the chiral system.

It is generally accepted that the doping of chiral materials with achiral molecules diminishes the chirality of the system. Here we report the opposite phenomenon. It was found that the structural chirality of smectic phases made of rodlike molecules, Sm-C(*) or Sm-C(*)(A) phases, measured as the reverse length of the helical pitch, is enhanced by adding small amount of achiral bent-shaped molecules. The effect is due to the chirality transfer between host and guest systems. Achiral bent-shaped molecules become structurally chiral due to the interactions with the chiral host that induces tilt and polar order of bent-shaped molecules. This induced chirality is then transferred back to the host.

Journal Article↗

The agonist of the protease-activated receptor-1 (PAR) but not PAR3 mimics thrombin-induced vascular endothelial growth factor release in human smooth muscle cells.

Thrombin, a serine protease generated by the activation of the blood coagulation cascade following vessel injury, induces vascular endothelial growth factor-(VEGF) release. However, the molecular mechanism of thrombin-induced VEGF release is largely unknown. Anagonist of protease-activated receptor-i (PARI), SFLL-RNPNDKYEPF, mimicked thrombin-induced VEGF release in human vascular smooth muscle (HVSM) cells, as determined by enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, and Northern blotting. In contrast, the agonist of PAR3, TFR- GAP, did not affect VEGF release or expression. SFLL-RNPNDKYEPF, but not TFRGAP, up-regulated [Ca2-]i.Moreover, the calcium ionophone A23187 was found to trigger VEGF release in HVSM cells. Thrombin-inducedVEGF release was blocked by anti-thrombin, heparin, a synthetic thrombin receptor inhibitor E5510, the calcium chelator BAPTA, the protein kinase C inhibitor calphostin C, and the MEK1/2 inhibitor U0126. Thus, our data show that thrombin caused VEGF release via PARI activation in a manner dependent on [Ca2+]i and p44/42 downstream from the receptor activation.

Base Sequence↗

NF-kappaB activation in peripheral blood mononuclear cells in neonatal asphyxia.

Neonatal asphyxia results in hypoxic-ischaemic encephalopathy. Previous studies have demonstrated that brain hypoxia and ischaemia lead to the production of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6. Transcription factor NF-kappaB is essential for the expression of these cytokines. We examined whether or not NF-kappaB is activated in peripheral mononuclear cells (PBMC) in neonatal asphyxia by flow cytometry. In addition, we examined the relationship between NF-kappaB activation in PBMC and the neurological prognosis. Flow cytometry analysis demonstrated that the level of NF-kappaB activation in CD14+ monocytes/macrophages of the patients with asphyxia who had neurological sequelae was significantly higher than in the controls, and in the patients with asphyxia who survived (31.7 +/- 7.2%versus 2.5 +/- 0.9%, P = 0.008, and versus 1.6 +/- 1.4%, P = 0.014, respectively). Our findings suggest that NF-kappaB activation in peripheral blood CD14+ monocytes/macrophages in neonatal asphyxia is important for predicting the subsequent neurological sequelae.

Asphyxia Neonatorum↗

Association of histochemical expression of Maackia amurensis leukoagglutinin-positive glycoconjugates with behaviour of human gastric cancer.

AIMS: To investigate the relationship between sialylation of glycoconjugates and clinicopathological characteristics of gastric cancer. METHODS AND RESULTS: Sialylation of glycoconjugates was examined histochemically in 71 gastric cancers using Maackia amurensis leukoagglutinin (MAL), a lectin that recognizes the trisaccharide sequence NeuAc alpha 2,3Gal beta 1,4GlcNAc/Glc. Positive staining with MAL was observed in the tumour region of all of the samples, but the populations of MAL-positive tumour cells in the tumour region varied among the samples. In the corresponding non-cancerous regions, however, no positive staining was observed. Calculating the percentage of MAL-positive tumour cells as part of the total tumour cells with respect to the MAL-staining index (MI) allowed the gastric cancer to be classified into two distinct groups: high and low levels of MI, with a cut-off level of 40% of MI. Furthermore, statistical analyses using the MI level and clinicopathological characteristics of the tumour indicated that a high MI level in gastric tumour tissues is related to a poorer prognosis. CONCLUSIONS: The appearance of MAL-positive glycoconjugates in gastric tumour cells is associated with the behaviour of gastric cancer.

Adult↗

Length of the occlusal glide during chewing in children with primary dentition.

Chewing is one of the most important functions of the mandible, but, to date, there are very few studies of this function in children. The purpose of this study was to quantify the length of the occlusal glide at the lower incisal point during gum chewing in children with primary dentition. Eleven girls with primary dentition were selected for this study. Mandibular excursions with occlusal contacts and gum chewing movement were measured using an optoelectronic system that can measure mandibular movement with six degrees-of-freedom at a sampling frequency of 100 Hz. A curved mesh diagram of incisor coordinates during mandibular excursions was established to calculate the length of the occlusal glide for each subject. The occlusal glide lengths of children were compared with previously reported results for adults. The estimated length of the occlusal glide during closing was significantly shorter in children than in adults, contrary to that during opening. This result suggests that children have a characteristic chewing pattern that differs from adults.

Adult↗