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Chain dimension of polystyrenes diluted with low molecular-weight homologues in semi-dilute solutions was investigated, referring to the results for solutions in benzene and styrene monomer, and its concentration dependence was clarified by small-angle neutron scattering (SANS) with a “contrast-matching” method. The styrene monomer was found to act as a good solvent comparable to benzene. The polystyrene was confirmed to expand in the bulk “diluent” homologues having sufficiently low molecular-weights, and its concentration dependence of expansion factor, α, became weaker with increasing the degree of polymerization, NS, of the short “diluent” polymer. The critical NS value, NS,c, which is defined as the maximum value to give excluded volume effects, was much higher than the earlier theoretical prediction by de Gennes, i.e., N S , c ∼ N L 1 / 2 , where NL is the degree of polymerization of the long “solute” polymer. The power law exponent for NS-dependence of α seems to follow −1/16, rather than −1/8 predicted by the scaling, suggesting that screening blob size, ξ, can be scaled as ξ ∼ N S 1 / 2 , which is equivalent to the radius of gyration for the “diluent” polymers.

Flow-Induced Structure and Viscoelastic Properties of Poly(styrene- block -2-vinylpyridine)s Solutions near the Order–Disorder Transition

To investigate the inhibitory effect of cyclosporin A on p-glycoprotein function in peripheral nerves (VIIth, VIIIth and sciatic nerves).Male mdr1a(-/-) and mdr1a(+/+) FVB mice were used. Doxorubicin (30 mg/kg) was administered intravenously with or without i.p. administration of cyclosporin A (200 mg/kg). Vinblastine (5 mg/kg) was also administered intravenously with or without i.p. administration of cyclosporin A (200 mg/kg).Tissue concentrations of doxorubicin and vinblastine in peripheral nerves of the mdr1a(+/+) mice pretreated with 200 mg/kg cyclosporin A were significantly higher than those in the mdr1a(+/+) mice administered doxorubicin or vinblastine alone, suggesting that cyclosporin A inhibited the efflux pump function of p-glycoprotein in the peripheral nerves. In the mdr1a(-/-) mice, tissue concentrations of doxorubicin and vinblastine in peripheral nerves were also significantly higher than those in the mdr1a(+/+) mice administered doxorubicin or vinblastine alone. Based on these results, it is suggested that p-glycoprotein plays an important role in blood-nerve barrier function by preventing side-effects induced by neurotoxic drugs.When doxorubicin and vinblastine are co-administered with cyclosporin A, the patient should be carefully monitored because peripheral nerve disorders may be induced.

We investigated the expression and function of mdr1a p-glycoprotein in peripheral nerves, including the VIIth and VIIIth nerves, using mdr1a p-glycoprotein gene knockout mice [mdr1a(-/-) mice] and wild-type mdr1a(+/+) mice. P-glycoprotein expression in capillary endothelial cells of the peripheral nerve tissues was detected by immunohistochemical and RT-PCR analyses in mdr1a(+/+) mice but not in mdr1a(-/-) mice. Pharmacokinetic analyses indicated that, compared to mdr1a(+/+) mice, mdr1a(-/-) mice showed a significantly higher accumulation of p-glycoprotein substrate drugs such as vinblastine and doxorubicin, which are neurotoxic. Tissue concentrations of vinblastine and doxorubicin were lower in the order of the brain, peripheral nerves and most other organs. However, increased accumulation was not detected after administering another neurotoxic drug, cisplatin, indicating that p-glycoprotein is selective at extruding drugs. These data indicate that mdr1a p-glycoprotein, which acts as an efflux pump, might play an important role in the blood-nerve barrier to prevent side effects induced by neurotoxic p-glycoprotein substrate drugs. The participation of p-glycoprotein in the blood-nerve barrier is considered to represent a new functional mechanism of this barrier.

Although doxorubicin [adriamycin (ADM)] ototoxicity has not been detected to date, it has been reported that neurotoxicity in the central nervous system was induced by chemotherapy with ADM in patients receiving chronic cyclosporin A (CsA) treatment. ADM ototoxicity may be induced by combination therapy with CsA because extrusion of ADM from the inner ear by p-glycoprotein (p-gp), which acts as an extrusion pump and is expressed on the surface of endothelial cells of capillary blood vessels, might be inhibited by CsA. resulting in significant accumulation of ADM in the inner ear. ADM (10 mg/kg) was administered to FVB mice either with or without CsA (200 mg/kg). Auditory brainstem responses (ABRs) were recorded before and after treatment. ABR changes were not observed in mice treated with either ADM or CsA alone. Threshold elevation, elongation of wave I-V latencies and interpeak latencies of waves I-II, I-III, I-IV and I-V were detected in mice treated with ADM in combination with CsA. These changes reached their peak values 3 weeks after treatment, and then recovered to pre-treatment levels. In normal mice, ADM is extruded by p-gp from the inner ear and auditory pathway, thus preventing hearing disorder. However, ADM ototoxicity was induced by combination therapy with CsA, indicating that CsA has an inhibitory action on p-gp function in the auditory pathway, including the inner ear. After organ transplantation, therefore, clinical administration of ADM in combination with CsA should be performed with caution.

Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine, regulates the proliferation and differentiation of granulocytic progenitor cells and functionally activated mature neutrophils. G-CSF also affects nonhematopoietic tumor cells through its binding to the specific receptor (G-CSFR) on the cells. The type IV collagenase [matrix metalloproteinase 2 (MMP-2)] is known to play a main role in the process of invasion and metastasis, but its regulation, for example, in expression or in activation, is not clearly understood. In this study, we investigated the role of G-CSF in the regulation of tumor cell invasion and the synthesis of MMP-2. G-CSFs producing the head and neck carcinoma cell line T3M-1 cells with metastatic ability and no G-CSF receptor (G-CSFR) expression were transfected with G-CSFR expression vector. In vitro treatment of G-CSFR-transfectant T3M-1 cells with recombinant G-CSF (rG-CSF) significantly augmented their invasive potential in a reconstituted basement membrane (Matrigel) system compared with that of parental cells. Moreover, MMP-2 activity of G-CSFR-transfectant T3M-1 cells was enhanced by the stimulation with rG-CSF, as assessed by gelatin zymography. These results identify G-CSF as a regulator of MMP-2 and cellular invasion.

Rheological properties of three immiscible polyisoprene (PI)/polydimethylsiloxane (PDMS) blends (PI:PDMS=1:9 by weight) having viscosity ratios ηd/ηm=0.155, 0.826, and 4.02, where ηd and ηm are the viscosities of the droplet and matrix, were investigated by directly measuring the droplet size distributions with a video microscope. Steady state measurements were performed by sequentially stepping up the shear rate γ (step-up) and step decrease (step-down) of the shear rate. Dynamic frequency sweep measurements were also performed immediately following cessation of steady shear flow. In the step-up measurements for blends with ηd/ηm=0.155 and 0.826, stresses were proportional to γ and the droplet sizes were well regulated by the flow and inversely proportional to γ for γ⩾0.553 s−1, in good agreement with the Doi–Ohta model [J. Chem. Phys. 95, 1242–1248 (1991)]. The results of step-down measurements were consistent with dynamic moduli measurements, because the droplet sizes were almost unchanged during these measurements. The results are in accord with Palierne’s model [Rheol. Acta 29, 204–214 (1990)]. For the ηd/ηm=4.02 blend, however, the droplet sizes were insensitive to γ, resulting in worse agreement between the experimental and theoretical results than for the other blends.Rheological properties of three immiscible polyisoprene (PI)/polydimethylsiloxane (PDMS) blends (PI:PDMS=1:9 by weight) having viscosity ratios ηd/ηm=0.155, 0.826, and 4.02, where ηd and ηm are the viscosities of the droplet and matrix, were investigated by directly measuring the droplet size distributions with a video microscope. Steady state measurements were performed by sequentially stepping up the shear rate γ (step-up) and step decrease (step-down) of the shear rate. Dynamic frequency sweep measurements were also performed immediately following cessation of steady shear flow. In the step-up measurements for blends with ηd/ηm=0.155 and 0.826, stresses were proportional to γ and the droplet sizes were well regulated by the flow and inversely proportional to γ for γ⩾0.553 s−1, in good agreement with the Doi–Ohta model [J. Chem. Phys. 95, 1242–1248 (1991)]. The results of step-down measurements were consistent with dynamic moduli measurements, because the droplet sizes were almost unchanged during t...

To examine the scaling relation proposed for textured materials, viscoelastic properties of binary mixtures of immiscible Newtonian fluids were measured in steady shear flows and in the transient states after step changes of the shear rate. The sample was a mixture of silicone oil and resin oil, which have almost equal density and viscosity. It was observed that (i) the shear stress and the first normal stress difference, under the steady shear flows, are almost proportional to the shear rate, and that (ii) the plots of the scaled transient stresses after a step change of shear rate, against the scaled strain, compose a single curve. These results can be well explained by the scaling relation. However, the shape of the transient stress curves after step changes of shear rate do not agree with that predicted by the constitutive equation proposed by Doi and Ohta.

In the present study we examined the expression of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells and investigated their possible role in the human NK-cell phenomenon. The incubation of either peripheral-blood lymphocytes (PBL) or large granular lymphocytes (LGL) with swainsonine (SW), an inhibitor of mannosidase II, resulted in the augmentation of cytotoxicity against K562 leukemia cells. The enhanced cytotoxicity was associated with increased binding of fluorescein isothiocyanate-conjugated Con-A to SW-treated effector cells, and immunofluorescence staining of the target K562 cells using goat anti-Con-A antibody (Ab) showed a significant positive shift in the flow cytometric pattern. Electrophoretic separation and immunoblotting analysis revealed that 4 components with a molecular weight of approximately 95, 80, 60 and 50 kDa were recognized by anti-Con-A Ab from the detergent-extract of K562 cells. The addition of Con-A during the antibody incubation step of the Western blotting abolished their expression, thus excluding non-specific binding of the antibody. The addition of Con-A also strongly inhibited the cytotoxicity of SW-treated effector cells (PBL or LGL) against K562 cells, and this inhibition was abolished by 40 mM alpha-methyl-mannopyranoside (alpha-MM), which binds to Con-A. Furthermore, Con-A increased the binding frequency of SW-treated LGL to K562, in spite of the inhibited cytotoxicity, and this effect could be neutralized by the further addition of alpha-MM. Our results suggest that Con A-like molecules might play an important role in cell-cell interactions between SW-treated effector cells and NK target cells.

Published theoretical equations for the sedimentation coefficient and intrinsic viscosity of a semiflexible chain are compared, neglecting the excluded volume effect. The theories are extended to the case of a small excluded volume, by applying the perturbation theory, established for flexible chains, to a semiflexible chain. Using the derived equation, the experimental results for the sedimentation coefficient and intrinsic viscosity of DNA and cellulose trinitrate are analyzed.

Under the physical requirement that the contour length of a polymer molecule remains constant irrespective of shear rate in the Rouse and Zimm theories and the Harris–Hearst theory, the shear rate dependence of intrinsic viscosity, flow birefringence, flow dichroism, normal stresses, the relaxation of flow birefringence and flow dichroism, and some quantities at zero shear rate have been calculated for molecules of different stiffness ranging from the rod to the flexible coil in θ solvents. Changes of hydrodynamic interaction with shear rate are not included. Comparing the present theory with the experimental results there is satisfactory agreement for stiff molecules such as the cellulose derivatives and DNA at low shear.