beta-Adrenergic receptor desensitization stimulates glucose uptake in C6 rat glioma cells

When C₆ glioma cells were stimulated by β -adrenergic ligands, [³H]-deoxyglucose uptake by the cells decreased in the first 30 min, followed by its acceleration. The stimulation of deoxyglucose uptake was attributable to desensitization of β-adrenergic receptor-adenylate cyclase system. When the cells were treated with quinacrine or tetracaine, phospholipase inhibitors, the stimulation of deoxyglucose uptake by isoproterenol was diminished without changing the basal rate. On the other hand, when C₆ glioma cells were treated with melittin or phorbol ester, phospholipase A₂ activators, the deoxyglucose uptake increases even in the absence of isoproterenol. Since these compounds inhibit or enhance phospholipase A₂ as well as the desensitization of β -adrenergic receptors (Proc. Natl. Acad. Sci. USA 77, 1341–1345, 1980), these results suggest that turnovers of phospholipids in the vicinity of β -adrenergic receptors modify the glucose uptake of C₆ glioma cells.     

Genetic differentiation between two types of dark chub,Zacco temmincki,in Japan

Two types of the dark chub,Zacco temmincki, collected from 10 river systems in Japan were genetically characterized at 27 protein coding loci using starch-gel electrophoresis. They were fixed for different alleles at 13 loci. No hybrid individuals were observed, even in specimens collected in stations where both types appear sympatrically, indicating that each type of the dark chub represents a distinct species.     

Modulatory effects of oligodendrocytes on the conduction velocity of action potentials along axons in the alveus of the rat hippocampal CA1 region

Like neurons and astrocytes, oligodendrocytes have a variety of neurotransmitter receptors and ion channels. However, except for facilitating the rapid conduction of action potentials by forming myelin and buffering extracellular K(+), little is known about the direct involvement of oligodendrocytes in neuronal activities. To investigate their physiological roles, we focused on oligodendrocytes in the alveus of the rat hippocampal CA1 region. These cells were found to respond to exogenously applied glutamate by depolarization through N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors. Electrical stimulation of the border between the alveus and stratum oriens evoked inward currents through several routes involving glutamate receptors and inward rectifier K(+) channels. Moreover, electrical stimulation resembling in vivo activity evoked long-lasting depolarization. To examine the modulatory effects of oligodendrocytes on neuronal activities, we performed dual, whole-cell recording on CA1 pyramidal neurons and oligodendrocytes. Direct depolarization of oligodendrocytes shortened the latencies of action potentials evoked by antidromic stimulation. These results indicate that oligodendrocytes increase the conduction velocity of action potentials by a mechanism additional to saltatory conduction, and that they have active roles in information processing in the brain.     

Oocyte mitochondria: Strategies to improve embryogenesis

Mitochondria play a central role to provide ATP for fertilization and preimplantation embryo development in the ooplasm. The mitochondrial dysfunction of oocyte has been proposed as one of the causes of high levels of developmental retardation and arrest that occur in preimplantation embryos generated using Assisted Reproductive Technology. Cytoplasmic transfer (CT) from a donor to a recipient oocyte has been applied to infertility due to dysfunctional ooplasm, with resulting pregnancies and births. However, neither the efficacy nor safety of this procedure has been appropriately investigated. In order to improve embryogenesis, we observed the mitochondrial distribution in ooplasma under the several conditions using mitochondrial GFP-transgenic mice (mtGFP-tg mice) in which the mitochondria are visualized by GFP. In this report, we will present our research about the mitochondrial distribution in ooplasm during early embryogenesis and the fate of injected donor mitochondria after CT using mtGFP-tg mice. The mitochondria in ooplasm from the germinal vesicle stage to the morula stage were accumulated in the perinuclear region. The mitochondria of the mtGFP-tg mouse oocyte transferred into the wild type mouse embryo could be observed until the blastocysts stage, suggesting that the mtGFP-tg mice oocyte is very useful for visual observation of the mitochondrial distribution in the oocyte, and that the aberrant early developmental competences due to the oocyte mitochondrial dysfunction may be overcome by transferring the "normal" mitochondria.     

Ceriporic acid C, a hexadecenylitaconate produced by a lignin-degrading fungus, Ceriporiopsis subvermispora

A lignin-degrading basidiomycete, Ceriporiopsis subvermispora produces a series of alkyl- and alkenylitaconates (ceriporic acids). Previously, two alkylitaconic acids with tetradecyl and hexadecyl side chains were isolated and identified as 1-heptadecene-2,3-dicarboxylic acid (ceriporic acid A) and 1-nonadecene-2,3-dicarboxylic acid (ceriporic acid B). In the present study, one hexadecenylitaconate (ceriporic acid C) was isolated and its chemical structure was analyzed by glycolation and subsequent (1) trimethylsilation, or (2) acetalation with acetone and acetone-d6. Analyses of the isolated metabolite demonstrated that the hexadecenylitaconic acid was (Z)-1,10-nonadecadiene-2,3-dicarboxylic acid. The structure of the side chain in ceriporic acid C was the same as that of hexadecenylcitraconate, chaetomellic acid B. Thus, it was found that ceriporic acids share close structural similarity with alk(en)yl citraconate derivatives, chaetomellic acids and other lichen lactones, protolichesterinic, lichesterinic, and murolic acids.     

Construction of humanized anti-ganglioside monoclonal antibodies with potent immune effector functions

 Gangliosides GD3, GD2 and GM2, which are the major gangliosides expressed on most human cancers of neuroectodermal and epithelial origin, have been focused on as effective targets for passive immunotherapy with monoclonal antibodies. We previously developed a chimeric anti-GD3 mAb, KM871, and a humanized anti-GM2 mAb, KM8969, which specifically bound to the respective antigen with high affinity and showed potent immune effector functions. Humanization of anti-ganglioside antibody is expected to enhance its use for human cancer therapy. In the present study, we generated a chimeric anti-GD2 mAb, KM1138, and further developed the humanized form of anti-GD2 and anti-GD3 mAbs by the complementarity-determining regions grafting method. The resultant humanized anti-GD2 mAb, KM8138, and anti-GD3 mAb, KM8871, showed binding affinity and specificity similar to those of their chimeric counterparts. In addition, both humanized mAbs had functional potency comparable to the chimeric mAbs in mediating the immune effector functions, consisting of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The production of these humanized anti-ganglioside mAbs, with potent effector functions and low immunogenicity, precedes the evaluation of the therapeutic value of anti-ganglioside mAbs in passive immunotherapy and the target validation for ganglioside-based vaccine therapy. Received: 30 November 2000 / Accepted: 30 January 2001     

Investigating the Influence of Visual Function and Systemic Risk Factors on Falls and Injurious Falls in Glaucoma Using the Structural Equation Modeling

Purpose

To investigate the relationship between visual function and the risks of falling and injurious falls in subjects with primary open angle glaucoma (POAG)

Methods

Questionnaires were conducted in 365 POAG patients to assess history of falls and falls with injury and general patient health. Structural equation modeling (SEM) was used to investigate the relationship between visual function, as measured by a patient’s binocular integrated visual field and visual acuity (VA), general health and the risks of falling and injurious falls.

Results

Among the 365 subjects, 55 subjects experienced falls in the past year. A significant difference was observed in worse-eye VA between the faller and non-faller groups (p = 0.03). SEM of fallers obtained a Root Mean Square Error of Approximation (RMSEA) of 0.035 and a Comparative Fit Index (CFI) of 0.99. The 95% confidence intervals (CI) of regression coefficients from this model suggested better VA and worse VA were significant risk factors for falling. Among the 55 fallers, 22 subjects experienced an associated injury. There was a significant difference in gender between the non-injurious and injurious faller groups (p = 0.002). SEM of injurious fallers obtained a RMSEA of 0.074 and a CFI of 0.97. In this SEM model, the 95% CI of regression coefficients suggested gender and average total deviation values in the lower peripheral visual field were significant risk factors for an injurious fall.

Conclusions

This study suggests that worse-eye and better-eye VAs are associated with falls. Furthermore, patients with inferior visual field loss and females were found to be at greater risk of injurious falls.