Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes

The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10(-4)mol/l, ketanserin at 10(-4) and 10(-8)-10(-10)mol/l and methiotepine at 10(-4) and 10(-6)-10(-8)mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration.     

Secondary web-flange interaction in framed-tube buildings

In the conventional plane-frame model of framed-tube buildings, only the primary interaction between the web frame and the flange frame is considered, through vertical shear transfer at corner columns. In addition to this, a secondary interaction takes place due to horizontal shear transfer at each floor level, through the floor slab having high in-plane rigidity. This interaction causes a discrepancy in member forces of a few bottom and top storeys. A simple modification is suggested in the form of an additional cantilever column connected to the conventional plane-frame model by axial force transfer members at every floor level. The improved model yields member forces in all the storeys that are very close to those obtained using 3D analysis.     

Restenosis and arterial remodelling after coronary angioplasty

Restenosis after coronary angioplasty (PTCA) is a complex process and is still the major problem, despite improvements in equipment and technique. Thrombus formation and intimal hyperplasia have been considered to be the main causes of the development of restenosis after primary successful angioplasty. As yet, pharmacological trials to prevent restenosis have failed to prevent it, despite the fact that the therapy has been aimed at reducing thrombus formation and intimal hyperplasia. Several new angioplasty devices have been developed. Series of observations and a few controlled trials have demonstrated restenosis rates similar to those obtained with conventional balloon angioplasty, except in the case of stent implantation, which appears to be promising. Intravascular ultrasound studies have provided new insight and a more complete understanding of the process leading to restenosis. Vascular remodeling is now considered as an important pathogenetic factor. It consists of a change in the cross-sectional vessel area and may involve an actual constriction of the artery. This may lead to lumen-narrowing and finally restenosis with minimal neointimal formation. In this review we summarise the literature on the restenosis process and the current status of the clinical trials aimed at preventing restenosis.     

Characterization of expression of phosphofructokinase isoforms in isolated rat pancreatic islets and purified beta cells and cloning and expression of the rat phosphofructokinase-A isoform

We prepared polymers having a phospholipid polar group, poly [omega-methacryloyloxyalkyl phosphorylcholine (MAPC)-co-n-butyl methacrylate(BMA)], as new biomedical materials and evaluated their blood compatibility with attention to protein adsorption and platelet adhesion. The total amount of proteins adsorbed on the polymer surface from human plasma was determined, and the distribution of adsorbed proteins on the plasma-contacting surface was analyzed. The amount of proteins adsorbed on every poly (MAPC-co-BMA) was small compared with that observed on polymers without the phospholipid polar group. However, there was no significant difference in the amount of adsorbed proteins on the poly(MAPC-co-BMA) even when the methylene chain length between the phospholipid polar group and the backbone in the MAPC moiety was altered. Platelet adhesion on the polymer surface from a platelet suspension in a buffered solution was evaluated with and without plasma treatment on the surface. When a rabbit platelet suspension was brought into contact with the poly(BMA) surface after treatment with plasma, many platelets adhered and aggregated. However, a reduced amount of platelet adhered on the poly(BMA) was found in the case of direct contact with the platelet suspension. On the other hand, the poly(MAPC-co-BMA)s could inhibit platelet adhesion under both conditions. Based on these results, it can be concluded that the proteins adsorbed on the surface play an important role in determining the platelet adhesion and suppression of the protein adsorption on the surface, which is one of the most significant ways of inhibiting platelet adhesion.     

A one-site, two-state model for the binding of anions in photosystem II

Photosystem II membranes, dialyzed against a Cl(-)-free buffer to remove bound Cl-, lost about 65% of the control activity. A light-intensity study of the Cl(-)-free membranes showed that all PS II centers were able to evolve oxygen at about 35% of the control rate when measured in Cl(-)-free medium. The Cl(-)-depleted membranes were immediately (< 15 s) reactivated to 85-90% of the original activity by the addition of fairly high concentrations of Cl- (Kd = 0.5 mM), but both Cl- and the activity were promptly lost when the membranes immediately after reactivation were diluted in a Cl(-)-free medium. However, stabilization of Cl(-)-binding could be accomplished by prolonged incubation in the presence of Cl-. The transition to stable binding, followed using 36Cl-, occurred over several minutes. The stable binding was further characterized by a Kd of 20 microM and a t1/2 for dissociation of about 1h [Lindberg et al. (1993) Photosynth. Res. 38, 401-408]. The effects on S2 signals of removal of Cl- were studied using EPR. The depletion of Cl- was accompanied by a shift in intensity toward the g = 4.1 signal at the expense of the multiline signal. When Cl- or Br- but not F- was added to the depleted PS II membranes, the original distribution of the signals was immediately (< 30 s) restored. We propose that Cl(-)-binding responsible for high oxygen-evolution activity and normal EPR properties of the S2 state may occur either as high affinity (Kd = 20 microM) and slowly exchanging (t1/2 = 1 h), or as low affinity (Kd = 0.5 mM) and rapidly exchanging (t1/2 < 15 s). Our results suggest that Br- but not F- has a mode of binding similar to that of Cl-. The high-affinity state is the normal state of binding, but once Cl- has been removed, it will first rebind as low-affinity, rapidly exchanging followed by conversion into a high-affinity, slowly exchanging mode of binding.     

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.     

Accumulation of ochratoxin A in rat kidney in vivo and in cultivated renal epithelial cells in vitro

Biological applications of triplex forming oligonucleotides will require the development of oligomers with high avidity and specificity. We examined the binding enhancement resulting from intercalator conjugation to both parallel design (polythymidine T15) and antiparallel design (polypurine AG15, for binding a 15 base pair polypurine-polypyrimidine sequence in the IL-2R alpha gene enhancer) oligomers under various ionic strength and temperature conditions. Oligonucleotides were conjugated through a urea link to 6,9 diamino-3-methoxy acridine (to give T15C and AG15C). Intercalator conjugation dramatically enhanced the specific triplex binding avidity (Kd = 5 nM for AG15C and 275 nM for T15C at 25 degrees C, compared to 2 microM for AG15 and > 50 microM for T15 at 25 degrees C), without detectable binding to an inappropriate target sequence. Surprisingly, triplex formation with AG15C occurred at lower Mg2+ concentrations than with T15C. AG15 and AG15C showed rapid Mg2+ dependent self association, but not T15C or T15. T15C triplex formation occurred rapidly (completion in less than 4 min), while AG15C bound to its target sequence more slowly over 20-24 h. Thus, binding constants in the low nanomolar range are now achievable with intercalator conjugated polypurine antiparallel binding oligonucleotides, a prerequisite for biological applications of such agents.     

High-power GaInP-AlGaInP quantum-well lasers grown by solid source molecular beam epitaxy

AlGaInP-based quantum-well laser diodes operating at wavelengths near 680 nm have been grown by all solid source molecular beam epitaxy (SSMBE). The lowest room temperature threshold current densities obtained from shallow ridge structures were 300 A/cm/sup 2/ and 330 A/cm/sup 2/ for pulsed and continuous wave operation, respectively. The dependences of the differential quantum efficiency and threshold current density on the cavity length were also studied in this preliminary SSMBE work. The internal quantum efficiency of 87-89% and the internal losses of 7-10 cm/sup -1/ were obtained.