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Biomedical subjects

T Kadoya

Publications and source records attributed to T Kadoya.

At least 19 recordsLinked to original sources

Development of torsade de pointes caused by exacerbation of QT prolongation during clipping of cerebral artery aneurysm in a patient with subarachnoid haemorrhage.

We report the case of a 79-yr-old woman with subarachnoid haemorrhage (SAH) in whom torsade de pointes (TdP) caused by worsening the QT prolongation occurred during clipping of cerebral artery aneurysm. This patient shows a potential risk of occurrence of life-threatening tachyarrhythmia, TdP by prolonging the QT interval during surgery in patients with SAH even with no additional factors that predispose to TdP. Therefore, a proper monitoring of the QT interval is necessary as a predictor of TdP. When ventricular tachyarrhythmia occurs, recognition of TdP is important because antiarrhythmic drug therapy for TdP is different from that for ventricular tachyarrhythmias that is not TdP.

Aged↗

Regulation of neuronal and glial galectin-1 expression by peripheral and central axotomy of rat primary afferent neurons.

Galectin-1 (Gal1) is an endogenously-expressed protein important for the embryonic development of the full complement of primary sensory neurons and their synaptic connections in the spinal cord. Gal1 also promotes axonal regeneration following peripheral nerve injury, but the regulation of Gal1 by axotomy in primary afferent neurons has not yet been examined. Here, we show by immunohistochemistry and in situ hybridization that Gal1 expression is differentially regulated by peripheral nerve injury and by dorsal rhizotomy. Following peripheral nerve injury, the proportion of Gal1-positive DRG neurons was increased. An increase in the proportion of large-diameter DRG neurons immunopositive for Gal1 was paralleled by an increase in the depth of immunoreactivity in the dorsal horn, where Gal1-positive terminals are normally restricted to laminae I and II. Dorsal rhizotomy did not affect the proportions of neurons containing Gal1 mRNA or protein, but did deplete the ipsilateral dorsal horn of Gal1 immunoreactivity, indicating that it is transported centrally by dorsal root axons. Dorsal rhizotomy also resulted in an increase in Gal1 mRNA the nerve peripheral to the PNS-CNS interface (likely within Schwann cells and/or macrophages), and to a lesser extent within deafferented spinal cord regions undergoing Wallerian degeneration. This latter increase was notable in the dorsal columns and along the prior trajectories of myelinated afferents into the deeper dorsal horn. These results show that neuronal and glial expressions of Gal1 are tightly correlated with regenerative success. Thus, the differential expression pattern of Gal1 following peripheral axotomy and dorsal rhizotomy suggests that endogenous Gal1 may be a factor important to the regenerative response of injured axons.

Analysis of Variance↗

Selective induction of DeltaFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of DeltaFosB and galectin-1 in neuroprotection and neurogenesis.

Transient forebrain ischemia causes selective induction of DeltaFosB, an AP-1 (activator protein-1) subunit, in cells within the ventricle wall or those in the dentate gyrus in the rat brain prior to neurogenesis, followed by induction of nestin, a marker for neuronal precursor cells, or galectin-1, a beta-galactoside sugar-binding lectin. The adenovirus-mediated expression of FosB or DeltaFosB induced expression of nestin, glial fibrillary acidic protein and galectin-1 in rat embryonic cortical cells. DeltaFosB-expressing cells exhibited a significantly higher survival and proliferation after the withdrawal of B27 supplement than the control or FosB-expressing cells. The decline in the DeltaFosB expression in the survivors enhanced the MAP2 expression. The expression of DeltaFosB in cells within the ventricle wall of the rat brain also resulted in an elevated expression of nestin. We therefore conclude that DeltaFosB can promote the proliferation of quiescent neuronal precursor cells, thus enhancing neurogenesis after transient forebrain ischemia.

Adenoviridae↗

Galectin-1 expression correlates with the regenerative potential of rubrospinal and spinal motoneurons.

Axotomized spinal motoneurons are able to regenerate to their peripheral targets, whereas injured rubrospinal neurons that lie completely within the CNS fail to regenerate. The differing cell body reactions to axotomy of these two neuronal populations have been implicated in their disparate regenerative ability. Recently, the lectin galectin-1 has been shown to be involved in both spinal motoneurons and primary afferent regeneration. Using in situ hybridization, we compared the endogenous galectin-1 mRNA expression in spinal motoneurons and rubrospinal neurons after axotomy. We found that 7 and 14 days after axotomy, galectin-1 mRNA increased in spinal motoneurons but decreased in rubrospinal neurons. Infusion of the brain-derived neurotrophic factor into the vicinity of the injured rubrospinal nucleus, which we have previously shown to increase the regenerative capacity of rubrospinal neurons, significantly increased galectin-1 mRNA compared with uninjured control levels. Thus, the expression of galectin-1 in neurons correlates with the regenerative propensity.

Analysis of Variance↗

DeltaFosB, but not FosB, induces delayed apoptosis independent of cell proliferation in the Rat1a embryo cell line.

The fates of Rat1a cells expressing FosB and DeltaFosB as fusion proteins (ER-FosB, ER-DeltaFosB) with the ligand binding domain of human estrogen receptor were examined. The binding of estrogen to the fusion proteins resulted in their nuclear translocation and triggered cell proliferation, and thereafter delayed cell death was observed only in cells expressing ER-DeltaFosB. The proliferation of Rat1a cells, but not cell death triggered by ER-DeltaFosB, was completely abolished by butyrolactone I, an inhibitor of cycline-dependent kinases, and was partly suppressed by antisense oligonucleotides against galectin-1, whose expression is induced after estrogen administration. The cell death was accompanied by the activation of caspase-3 and -9, the fragmentation of the nuclear genome and cytochrome c release from the mitochondria, and was suppressed by zDEVD-fmk and zLEHD-fmk but not zIETD-fmk. The cell death was not suppressed by exogenous His-PTD-Bcl-x(L) at all, suggesting involvement of a Bcl-x(L)-resistant pathway for cytochrome c release.

Animals↗

Positive pressure ventilation during fibreoptic intubation: comparison of the laryngeal mask airway, intubating laryngeal mask and endoscopy mask techniques.

BACKGROUND: The efficacy of delivery of mechanical ventilation through different airway devices during fibreoptic intubation is not known. METHODS: We compared the laryngeal mask airway (LMA), intubating laryngeal mask (ILM) and endoscopy mask for positive pressure ventilation (PPV) during fibreoptic intubation. In 80 adult paralysed patients, fibreoptic intubation was performed during PPV using a combination of a size 3 or 4 LMA with a 6.0 mm nasal RAE tracheal tube (LMA3/4 group; n=22), a size 5 LMA with a 7.0 mm nasal RAE tube (LMA5 group; n=18), an ILM with an 8.0 mm special reinforced tracheal tube (ILM group; n=20) or an endoscopy mask (Patil mask) with a 7.5 mm standard tracheal tube (Patil group; n=20). The inspiratory and expiratory tidal volumes (VI and VE) with a ventilation pressure of 20 cm H2O were measured using a pneumotachograph. RESULTS: Mean VE values during fibreoptic intubation in the LMA5 [5.3 (SD 1.5) ml kg(-1)] and ILM [7.1 (2.3) ml kg(-1)] groups were greater than in the LMA3/4 group [2.6 (1.0) ml kg(-1), P<0.0001]. The mean VE was greater in the Patil group [20.6 (4.9) ml kg(-1)] than in the other three groups (P<0.0001). Gastric insufflation during intubation was more frequent in the Patil group (30%) than in the other three groups (4.5-5.6%) (P<0.05). CONCLUSION: PPV is possible with the LMA, ILM or endoscopy mask during fibreoptic intubation. With an airway pressure of 20 cm H2O, ventilation during intubation using a size 3 or 4 LMA was almost insufficient, while ventilation using a size 5 LMA or an ILM was almost acceptable. Ventilation during intubation with the endoscopy mask was greater than that with the LMA or ILM, but gastric insufflation was more frequent.

Adult↗

Galectin-1 is a component of neurofilamentous lesions in sporadic and familial amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), abnormal accumulation of neurofilaments induces pathological changes such as axonal spheroids, cord-like neurite swellings, and perikaryal conglomerate inclusions in degenerating motor neurons of the spinal cord, and the accumulation seems to cause motor neuron degeneration in this disease. Such ALS lesions were intensely labeled with HepSS-1, a monoclonal antibody to heparan sulfate. Since the identification of HepSS-1-immunoreactive substance seems to be an important step for understanding the molecular pathology of ALS, we purified the substance from human spinal cord tissue to homogeneity. Amino acid sequence of the protein was consistent with that of galectin-1. Immunohistochemistry using antibodies against recombinant human galectin-1 showed that galectin-1 was accumulated in these lesions in ALS. Although HepSS-1 was believed to be specific for heparan sulfate, it reacted with recombinant human galectin-1 which has no heparan sulfate moiety. The results show that galectin-1 is a component of the neurofilamentous lesions in ALS. Since galectin-1 has axonal regeneration-enhancing activity, the abnormal accumulation of galectin-1 to the lesions seems to be related to the pathological process of ALS.

Aged↗

Inhibition of Wnt signaling pathway by a novel axin-binding protein.

Axin forms a complex with adenomatous polyposis coli gene product, glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, Dvl, and protein phosphatase 2A and functions as a scaffold protein in the Wnt signaling pathway. In the Axin complex, GSK-3beta efficiently phosphorylates beta-catenin, which is then ubiquitinated and degraded by proteasome. We isolated a novel protein that binds to Axin and named it Axam (for Axin associating molecule). Axam formed a complex with Axin in intact cells and bound directly to Axin. Axam inhibited the complex formation of Dvl with Axin and the activity of Dvl to suppress GSK-3beta-dependent phosphorylation of Axin. Furthermore, Axam induced the degradation of beta-catenin in SW480 cells and inhibited Wnt-dependent axis duplication in Xenopus embryos. These results suggest that Axam regulates the Wnt signaling pathway negatively by inhibiting the binding of Dvl to Axin.

Adaptor Proteins, Signal Transducing↗

Proteomic approach to the identification of cell membrane proteins.

The expression of plasma membrane proteins in human monocyte-derived U937 cells was examined by cell disruption and isolation of microsomal fractions. Two alternative procedures for cell disruption, Dounce homogenization and nitrogen cavitation, were compared. Cell homogenization and sequential centrifugation resulted in an approximately fivefold enrichment of plasma membrane proteins in the microsomal fraction. However, identification of 30 such apparently enriched proteins by two-dimensional (2-D) electrophoresis, proteolytic digestion, and mass spectrometry revealed that only eight were plasma membrane proteins, the remaining 22 being contaminants. In contrast, nitrogen cavitation followed by sequential centrifugation and solubilization of proteins with sodium dodecyl sulfate (SDS) and 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate (CHAPS) detergent yielded subcellular fractions, including microsomes, that showed little overlap in constituent proteins as revealed by 2-D electrophoresis. These results highlight the importance of obtaining pure plasma membranes and complete solubilization of membrane proteins for proteomic analysis.

Electrophoresis, Gel, Two-Dimensional↗

Identification of oxidized galectin-1 as an initial repair regulatory factor after axotomy in peripheral nerves.

Various neurotrophic factors that promote axonal regeneration have been investigated in vivo, but the signals that prompt the axons to send out processes in peripheral nerves after axotomy are not well understood. We have shown using two specific strategies that galectin-1 can play an important role in this initial stage. One used an in vitro nerve regeneration model that allowed us to monitor the initial axon and support cell outgrowth from the proximal nerve stump comparable to the initial stages of nerve repair. The other strategy was to clarify the axonal regeneration-promoting factor from kidney-derived cells. Using these strategies, we discovered that oxidized galectin-1 from the cell (COS1 cell) conditioned media acts as an axonal regeneration-promoting factor without the lectin activity. Oxidized recombinant human galectin-1 (rhGAL-1/Ox) showed the same activity at low concentrations (pg/ml range). A similarly low concentration also effectively promoted axonal regeneration in both transection and crush experiments in vivo. Moreover, the application of functional anti-galectin-1 antibody strongly inhibited the regeneration in vivo. Since galectin-1was shown to be secreted and localized in the regenerating sciatic nerve, this suggests that secreted galectin-1 may be oxidized and change its molecular structure to regulate initial repair after axotomy as a kind of cytokine.

Animals↗

A new method of predicting pulmonary capillary wedge pressure: the arterial pressure ratio.

The response of arterial blood pressure to an increase in intrathoracic pressure has been shown to be predictive of pulmonary capillary wedge pressure. We devised a new method, which we termed the arterial pressure ratio. We defined arterial pressure ratio as the ratio of systolic blood pressure of the final beat during the strain phase of the Valsalva manoeuvre to that during apnoea before the manoeuvre, and tested the accuracy of arterial pressure ratio in predicting pulmonary capillary wedge pressure. In 30 patients scheduled for elective abdominal aortic reconstruction, following induction of general anaesthesia and tracheal intubation, a 20-G catheter and pulmonary artery catheter were inserted through the radial artery and right internal jugular vein, respectively. Pulmonary capillary wedge pressure was then measured during a brief period of apnoea and the Valsalva manoeuvre was performed by application of pressure to the reservoir bag. Airway pressure was maintained at 30 cmH2O for 10 s and then released. Radial arterial pressure and airway pressure were recorded simultaneously, and arterial pressure ratio was calculated. There was a close linear correlation between arterial pressure ratio and pulmonary capillary wedge pressure (r = 0.88, p < 0.0001).

Aged↗

Oxidized galectin-1 promotes axonal regeneration in peripheral nerves but does not possess lectin properties.

Galectin-1 has recently been identified as a factor that regulates initial axonal growth in peripheral nerves after axotomy. Although galectin-1 is a well-known beta-galactoside-binding lectin, its potential to promote axonal regeneration as a lectin has not been reported. It is essential that the process of initial repair in peripheral nerves after axotomy is well clarified. We therefore undertook to investigate the relation between the structure and axonal regeneration-promoting activity of galectin-1. Recombinant human galectin-1 secreted into the culture supernatant of transfected COS1 cells (rhGAL-1/COS1) was purified under nonreducing conditions and subjected to structural analysis. Mass spectrometric analysis of peptide fragments from rhGAL-1/COS1 revealed that the secreted protein exists as an oxidized form containing three intramolecular disulfide bonds (Cys2-Cys130, Cys16-Cys88 and Cys42-Cys60). Recombinant human galectin-1 (rhGAL-1) and a galectin-1 mutant in which all six cysteine residues were replaced by serine (CSGAL-1) were expressed in and purified from Escherichia coli for further analysis; the purified rhGAL-1 was subjected to oxidation, which induced the same pattern of disulfide linkages as that observed in rhGAL-1/COS1. Oxidized rhGAL-1 enhanced axonal regeneration from the transected nerve sites of adult rat dorsal root ganglion explants with associated nerve stumps (5.0-5000 pg. mL-1), but it lacked lectin activity. In contrast, CSGAL-1 induced hemagglutination of rabbit erythrocytes but lacked axonal regeneration-promoting activity. These results indicate that galectin-1 promotes axonal regeneration only in the oxidized form containing three intramolecular disulfide bonds, not in the reduced form which exhibits lectin activity.

Animals↗