Inhibition of G1 cyclin expression in normal rat kidney cells by inostamycin, a phosphatidylinositol synthesis inhibitor

We previously reported that inostamycin, an inhibitor of CDP-DG: inositol transferase, inhibited cell proliferation in normal rat kidney (NRK) cells by blocking cell cycle progression at the G1 phase. In the present paper, we report the effect of inostamycin on the serum-induced activation of Ser/Thr protein kinases that are involved in G1 progression. In quiescent NRK cells mitogen-activated protein kinase (MAP kinase) and casein kinase II were activated within 15 min after serum addition. Neither activation was affected by the treatment with inostamycin. However, in the inostamycin-treated cell, cyclin-dependent kinase 2 (CDK2) failed to be activated after serum stimulation. Since serum-induced expression of cyclin E was also suppressed by inostamycin, this inhibitor would appear to block CDK2 activation by inhibiting cyclin E expression. Furthermore, inostamycin also inhibited cyclin D1 expression induced by serum; and consequently, hyperphosphorylation of retinoblastoma protein (pRB) by RB-kinases such as CDK4 and CDK2 was abolished, which would result in elimination of functional inactivation of pRB. Thus, early G1 arrest in NRK cells by inostamycin is due to the inhibition of cyclin D1 and E expressions.     

Small increase of CR1 and CR3 by C5a-receptors on polymorphonuclear leukocytes in systemic lupus erythematosus

One of the anaphylatoxins, C5a, is known to increase the expression of the complement receptors, CR1 and CR3, on PMNs which play important roles in the phagocytosis. We measured the expression of these receptors before and after the stimulation with C5a and C5a-receptors (C5aR) on PMNs in patients with systemic lupus erythematosus (SLE). PMNs from 16 patients and 11 normal controls were tested. All the patients with SLE were administered with prednisolone orally and were in the inactive stage. The CR1 expression in SLE was significantly weak (p < 0.01) before and after stimulation with 4.55 nM (50 micrograms/ml) of C5a. There was no significant difference of CR3 expression before stimulation. However, after the stimulation with C5a, the increase of CR3 on PMNs from SLE was significantly small (p < 0.01). C5aR on PMNs showed no difference between the two groups. However, the expression of C5aR was significantly suppressed in patients treated with a high dosage of prednisolone (> = 10 mg/day) compared to those with a low dosage of prednisolone (< 10 mg/day). There was no significant difference of CR1 and CR3 expression between these groups. It is concluded that the increase of CR1 and CR3 on PMNs by C5a in small in SLE, of which impaired increase is not due to C5aR on PMNs, and that the expression of C5aR is suppressed by prednisolone.     

High level expression of the homeobox gene HB24 in a human T-cell line confers the ability to form tumors in nude mice

Epidermal growth factor (EGF)-induced c-fos and c-jun expression is strongly suppressed in microgravity. We investigate here whether this is due to inhibition of processes occurring during the initiation of EGF-induced signal transduction. For this purpose, EGF-induced receptor clustering is used as a marker. The lateral distribution of EGF receptors is directly visualized at an ultrastructural level by the label-fracture method. Quantification of the receptor distributions shows that EGF-induced receptor redistribution is similar under normal and microgravity conditions. This suggests that microgravity influences EGF-induced signal transduction downstream of EGF binding and EGF receptor redistribution, but upstream of early gene expression in human A431 cells.     

Molecular cloning and characterization of rat lin-10

In Caenorhabditis elegans, the vulval induction is mediated by tyrosine kinase receptor/Ras signal transduction pathway composed of the lin-3, let-23, and let-60 products. In addition to these gene products, the lin-2, lin-7, and lin-10 products are also implicated in this pathway. Lin-2 encodes a MAGUK and lin-7 encodes a small protein with one PDZ domain. The lin-10 product has no homology to known proteins. Here, we have cloned a rat homologue of the lin-10 product and characterized it. Rat lin-10 is ubiquitously expressed in various rat tissues and distributed in both the cytosol and membrane fractions. In brain, however, rat lin-10 is distributed only in the membrane fraction and enriched in the synaptic plasma membrane and postsynaptic density fractions. These results suggest that rat lin-10 is involved at least in synaptic functions in brain.     

Strongyloidiasis associated with nephrotic syndrome

We report a nephrotic syndrome patient with eosinophilia who developed ileus, epigastralgia and malabsorption due to strongyloidiasis which became symptomatic by steroid therapy. The patient was then treated with thiabendazole and recovered. A percutaneous renal biopsy revealed minimal change nephrotic syndrome. This renal injury may be brought on by severe infection of Strongyloides stercoralis. It is important to rule out strongyloidiasis prior to corticosteroid therapy to patients from eosinophilia endemic areas.     

Gelation of poly(vinyl alcohol)/phenol/water solutions and gel spinning

The light transmittance of the gels of poly(vinyl alcohol) (PVA)/phenol/water solutions was examined for the entire range of phenol/water content. Excellent transparency was found for the gels with phenol contents of 70–95 vol %. In full consideration of the results for the transparency and melting temperature of the gels and the viscosity and gelation ability of solutions, the PVA solutions of 75 vol % phenol content were selected for the gel spinning. The maximum dynamic moduli of drawn filaments at 25°C (room temperature) were 42 GPa (15x) for atactic PVA and 45 GPa (14x) for syndiotacticity-rich PVA. © 1995 John Wiley & Sons, Inc.     

Design of new catalysts for ecological high-quality transportation fuels by combinatorial computational chemistry and tight-binding quantum chemical molecular dynamics approaches

Recently, we introduced a concept of combinatorial chemistry to computational chemistry and proposed a new method called “combinatorial computational chemistry”, which enables us to perform a theoretical high-throughput screening of catalysts. In the present paper, we reviewed our recent application of our combinatorial computational chemistry approach to the design of new catalysts for high-quality transportation fuels. By using our combinatorial computational chemistry techniques, we succeeded to predict new catalysts for methanol synthesis and Fischer–Tropsch synthesis. Moreover, we have succeeded in the development of chemical reaction dynamics simulator based on our original tight-binding quantum chemical molecular dynamics method. This program realizes more than 5000 times acceleration compared to the regular first-principles molecular dynamics method. Electronic- and atomic-level information on the catalytic reaction dynamics at reaction temperatures significantly contributes the catalyst design and development. Hence, we also summarized our recent applications of the above quantum chemical molecular dynamics method to the clarification of the methanol synthesis dynamics in this review.     

Graft polymerization of some vinyl monomers onto acrylic rubber. II. Mechanical properties of graft polymers

Some mechanical properties of styrene and acrylonitrile copolymers grafted onto acrylic rubber are investigated. The impact strength of graft polymers depended upon the nature and the concentration of the catalyst, the composition and the intrinsic viscosity of the rubber, and the acrylonitrile content in the rigid matrix. The most desirable result was obtained when benzoyl peroxide as the catalyst, n-butyl acrylate–acrylonitrile copolymer of 7–10% acrylonitrile content, and about 0–5% acrylonitrile in the rigid matrix were used. Dynamic mechanical tests show the increase in efficiency of rubber modification by the grafted chains. The better weathering resistance of these graft polymers, as compared with commercial ABS plastics, was confirmed.     

The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

Introduction : Topiroxostat, a recently developed xanthine oxidase inhibitor, is expected to have fewer adverse effects than allopurinol because it has different mechanism of action from alloprinol. However, its dosage, usage and safety have not been established in patients with impaired renal function or those undergoing dialysis at the development since no studies was conducted in these patients. Methods : Cross over clinical trial using 3 months of allopurinol and topiroxostat on 27 maintain Japanese HD patients were carried out. The effects on oxidative stress status of both drugs were also evaluated by measuring oxidation reduction potential. Findings : Twenty‐five of twenty‐seven patients completed study. The mean serum uric acid levels in the topiroxostat‐treated arm was significantly lower than it in the allopurinol‐treated arm time‐dependently (P < 0.0001). Corrected oxidative stress ratio defined as biological antioxidant potential/diacron reactive oxygen metabolites was significantly increased in topiroxostat‐arm (*P = 0.0035), but not in allopurinol‐arm (P = 0.1429). No significant difference was seen in diacron reactive oxygen metabolites, biological antioxidant potential, static oxidation‐reduction potential, and capacity oxidation‐reduction potential between pre and post treatment of both drugs. Discussion : It is suggested that a low dose of topiroxostat decreased serum uric acid sufficiently to maintain it below 7.0 mg/dL in patients receiving hemodialysis.