Kaneyuki Kawamae

Brain trauma induces expression of diacylglycerol kinase ζ in microglia

Diacylglycerol kinase (DGK) is an enzyme which phosphorylates a second messenger diacylglycerol and consists of a family of isozymes that differ in terms of structural motifs, enzymological property, and cell and tissue distribution. One of the isozymes, DGKzeta was originally shown to be expressed in various kinds of neurons under physiological conditions. However, we unexpectedly found that under pathological conditions, such as cerebral infarction, DGKzeta-immunoreactivity is detected in non-neuronal cells, although it remained to be elucidated in detail which cell types are responsible for the induced expression of DGKzeta in this setting. To further elucidate functional implications of DGKzeta in non-neuronal cells we performed detailed immunohistochemical analysis of DGKzeta using rat brain cryoinjury model. As early as 1h after cryoinjury, DGKzeta-immunoreactivity was greatly decreased in the afflicted cerebral cortex and almost disappeared in the necrotic core. On day 7 after cryoinjury, however, DGKzeta-immunoreactivity reappeared in this area. DGKzeta-immunoreactivity was clearly detected in Iba1-immunoreactive cells of an oval or ameboid shape in the scar region, which represent activated microglia and/or macrophages. On the other hand, DGKzeta-immunoreactivity was not detected in Iba1-immunoreactive, resting microglia of ramified and dendritic configuration in the intact cortex. Furthermore, DGKzeta-immunoreactive cells were also positive for a microglia marker GLUT5 in the scar region, but never for an astrocyte marker GFAP. Taken together, the present study reveals that DGKzeta is induced in activated microglia in brain trauma, suggesting the functional significance of DGKzeta in this process.

Corrigendum: A high-flow nasal cannula system set at relatively low flow effectively washes out CO2 from the anatomical dead space of a respiratory-system model

[This corrects the article on p. 105 in vol. 70, PMID: 28184277.].

Arachidonoyl-Specific Diacylglycerol Kinase ε and the Endoplasmic Reticulum

The endoplasmic reticulum (ER) comprises an interconnected membrane network, which is made up of lipid bilayer and associated proteins. This organelle plays a central role in the protein synthesis and sorting. In addition, it represents the synthetic machinery of phospholipids, the major constituents of the biological membrane. In this process, phosphatidic acid (PA) serves as a precursor of all phospholipids, suggesting that PA synthetic activity is closely associated with the ER function. One enzyme responsible for PA synthesis is diacylglycerol kinase (DGK) that phosphorylates diacylglycerol (DG) to PA. DGK is composed of a family of enzymes with distinct features assigned to each isozyme in terms of structure, enzymology, and subcellular localization. Of DGKs, DGKε uniquely exhibits substrate specificity toward arachidonate-containing DG and is shown to reside in the ER. Arachidonic acid, a precursor of bioactive eicosanoids, is usually acylated at the sn-2 position of phospholipids, being especially enriched in phosphoinositide. In this review, we focus on arachidonoyl-specific DGKε with respect to the historical context, molecular basis of the substrate specificity and ER-targeting, and functional implications in the ER.

Interabdominal analgesia in pain management after cholecystectomy: A preliminary report

In recent years, recognition of the importance of adequate postoperative pain relief has been increasing [13]. We usually perform epidural anesthesia for upper abdominal surgery. However, it is occasionally either impossible or too risky to place a catheter into the epidural space because of hemorrhagic diathesis, adhesion, or synostosis. Thus, we have developed a new technique as the sole treatment for postoperative pain in cholecytectomy patients which involves the insertion of an epidural catheter into the omental sac and the adminstration of local anesthetics. The results so far have been encouraging, and we feel that the method is worthy of description. We have termed this technique interabdominal analgesia (IAA).

DGKζ Downregulation Enhances Osteoclast Differentiation and Bone Resorption Activity Under Inflammatory Conditions.

Bone homeostasis is maintained by a balance between resorption of the bone matrix and its replacement by new bone. Osteoclasts play a crucially important role in bone metabolism. They are responsible for bone resorption under pathophysiological conditions. Differentiation of these cells, which are derived from bone marrow cells, depends on receptor activator of NF‐κB ligand (RANKL). RANKL‐induced osteoclastogenesis is regulated by the phosphoinositide (PI) signaling pathway, in which diacylglycerol (DG) serves as a second messenger in signal transduction. In this study, we examined the functional implications of DG kinase (DGK), an enzyme family responsible for DG metabolism, for osteoclast differentiation and activity. Of DGKs, DGKζ is most abundantly expressed in osteoclast precursors such as bone marrow‐derived monocytes/macrophages. During osteoclast differentiation from precursor cells, DGKζ is downregulated at the protein level. In this regard, we found that DGKζ deletion enhances osteoclast differentiation and bone resorption activity under inflammatory conditions in an animal model of osteolysis. Furthermore, DGKζ deficiency upregulates RANKL expression in response to TNFα stimulation. Collectively, results suggest that DGKζ is silent under normal conditions, but it serves as a negative regulator in osteoclast function under inflammatory conditions. Downregulation of DGKζ might be one factor predisposing a person to osteolytic bone destruction in pathological conditions. J. Cell. Physiol. 232: 617–624, 2017.

Development of a bronchospasm device model

AbstractThere is no strong evidence to support ventilatory management for critical limitation of expiratory flow, such as bronchospasm during anesthesia or an acute exacerbation of severe asthma and chronic obstructive pulmonary disease (COPD). Animal models cannot be used to develop reproducible experimental models for conducting mechanical ventilation strategy research relating to these etiologies due to the resulting respiratory and hemodynamic instabilities. Therefore, we developed a device model by modifying a positive end-expiratory pressure (PEEP) valve that can simulate the characteristics of airway bronchoconstriction (i.e., limited peak expiratory flow and a prolonged expiratory phase). These characteristics were found to improve upon narrowing the expiratory port. We believe that this device model will facilitate future mechanical ventilation experiments.

0232. Evaluation of HFNC'S wash out effect; a comparison of open- and closed-mouth models

Although clinical studies of the high-flow nasal cannula (HFNC) and its effect on positive end-expiratory pressure (PEEP) have been performed, the mechanism of the washout effect and its relation with HFNC flow have not been well evaluated. Therefore, we made a respiratory model that can exhale with controllable end-tidal PCO2 (PETCO2) to evaluate the washout effect of HFNC.Objective. To evaluate the quantitative results of HFNCs washout effect comparing open- and closed-mouth models.