Red blood cell glutathione status in patients with gastrointestinal malignancies treated with 5-fluorouracil

As an alternative to surgical splenectomy, partial splenic embolization was performed in seven children for hypersplenism manifested by splenomegaly, thrombocytopenia, leukopenia, and erythrocyte hemolysis. Within a few days, platelet and leukocyte counts rose significantly in all patients and were maintained in six of seven patients during a follow-up period of 9 to 69 months. Spleen size and abdominal distention also decreased significantly in all children. There were no infectious complications.     

Inhibition of acid secretion in gastric parietal cells by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93

A novel Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) inhibitor, KN-93 potently inhibits gastric acid secretion from parietal cells. As previously reported (1), treatment of parietal cells with a selective inhibitor of CaM kinase II, KN-62 resulted in the inhibition of cholinergic-stimulated rabbit parietal cell secretion, whereas it failed to inhibit the histamine and forskolin response. In contrast effects of carbachol, histamine and forskolin were significantly inhibited by KN-93 with an IC50 of 0.15, 0.3 and 1 microM, respectively; these effects occurred without any changes in intracellular cyclic AMP and Ca2+ levels. In the present study we investigated the mechanism by which KN-93 acts upon the acid-secreting machinery of gastric parietal cells. Neither redistribution of the proton pump activity nor the morphological transformation were affected by KN-93. The drug only weakly inhibited the H+, K(+)-ATPase activity but strongly dissipated the proton gradient formed in the gastric membrane vesicles and reduced the volume of luminal space. Thus KN-93 acts at pH gradient formation whereas KN-62 acts only at CaM Kinase II.     

HER-2/c-erbB2 is phosphorylated by calmodulin-dependent protein kinase II on a single site in the cytoplasmic tail at threonine-1172

Calmodulin-dependent protein kinase II (Cam kinase II) is known to desensitise epidermal growth factor receptor (HER-1) tyrosine kinase activity by a process involving phosphorylation at serines 1046/47 in the cytoplasmic tail. We have developed an experimental system to investigate phosphorylation of the related HER-2/c-erbB2 proto-oncogene utilising purified Cam kinase II and recombinant glutathione-S-transferase (GST) fusion proteins. The cDNA for rat Cam kinase II-alpha was transfected into human embryonic kidney (HEK) 293 fibroblasts and the expressed protein purified to homogeneity by calmodulin-agarose affinity chromatography. A GST fusion protein comprising residues 1126-1255 of HER-2 was phosphorylated by purified Cam kinase II, in contrast to a GST protein comprising residues 1005-1125. Phosphoamino-acid analysis and site-directed mutagenesis indicated that HER-2 was phosphorylated on a single site at threonine-1172 which resides within a consensus Cam kinase II phosphorylation site (RAKT). HER-2 (threonine-1172-alanine), in the form of a ligand-inducible chimaera HER-1/2, was co-transfected into HEK-293 fibroblasts with a constitutively active form of Cam kinase II, followed by in vivo labelling of these cells with 32 P-orthophosphate. Immunoprecipitation of ligand-activated receptors followed by two-dimensional phosphopeptide mapping indicated that threonine-1172 in HER-2 is a newly identified in vivo site which can be hyper-phosphorylated by constitutively active Cam kinase II. In addition, when over-expressed in HEK-293 fibroblasts, HER-1/2 (threonine-1172-alanine) showed a defect in desensitisation and underwent a more sustained EGF-induced receptor autophosphorylation compared to wild-type HER-1/2.     

Synthesis and characterisation of carboxylic acid and diphenylphosphine derivatives in the 1,3-diyne series: Spectral properties of polydiacetylene carboxylates

Symmetrically substituted 1,3-diynes containing hydroxyalkyl ( 1a-d ), bromoalkyl ( 1e-h ) (diphenylphosphinyl) ( 1i-k ) and carboxyalkyl ( 2a-d ) substituents have been prepared and characterised; the phosphine derivative ( 1k ) has been converted with alkyl iodides ( RI ; R = Me, Et) into bis(phosphonium) salts ( 1l and m ). During preparation of the diynedioic acid. ( 2a ), the non-centrosymmetrical diyne, HO₂CCH₂C?C—C?C(CH₂)₂OH ( 3 ), was also isolated. ⁶⁰Co γ-Irradiation of diacetylene monomers ( 2a – d ) and 10,12-tricosadiyn-1-oic acid gave the corresponding polydiacetylene derivatives ( 4a – d and 5 ), respectively. Rubidium salts of ( 4c ) and ( 4d ), a barium salt of ( 4c ), and a potassium salt of ( 5 ) were prepared and isolated; soluble potassium salts of the carboxylic acid polymers ( 4 ) were generated in aqueous solution. The effects of changes in pH on the UV/visible absorption spectra of aqueous solutions of selected carboxylic acid polydiacetylenes have been recorded, and are discussed.     

The short-term effect of a smoking prevention program for the upper graders of elementary schools--the results of intervention study for two years with quasi-experimental design

The purpose of this study was to evaluate the short-term effect of a smoking prevention program for Japanese elementary school-children in the fifth and sixth grades. The program was developed with concepts found in the Know Your Body Program and the conclusions of a National Cancer Institute-convened Expert Advisory Panel, and focused on teaching about the short-term effects of smoking and on resistance to social pressures to smoke. The study was conducted with a quasi-experimental design. An intervention group (52 boys and 54 girls) received three sessions for both the fifth grade in 1992 and the sixth grade in 1993. Moreover, the intervention group received a pre-test before the first session and a post-test after the third session in each grade. A comparison group (102 boys and 91 girls) received the same tests at the same time as the intervention group, but did not receive any program on smoking prevention. The short-term effect of the program were evaluated using the results of the pre-test in the fifth grade and of the post-test in the sixth grade in both groups. The results were as follows: 1) Remarkable short-term effects of the intervention were seen in respect to awareness of the importance of not smoking in girls, and also in the knowledge of the short-term effects of smoking in both sexes. 2) The intervention was not effective with respect to intention to smoke at the age of 20 and self-efficacy of refusing to smoke in both sexes. 3) The short-term effects were not clear in the smoking behavior in both sexes because the rates of ever smokers and of monthly smokers were almost the same for two years between the intervention group and the comparison group. 4) The smoking behaviors of children, their parents and their best friends had little influence on the results of the post-test in the sixth grade.     

Comparison of the periodic solution method with TRNSYS and SUNCODE for thermal building simulation

Based on periodic solutions of the governing heat conduction equations in a single zone building, computer software ADMIT has been developed for thermal simulation of buildings. Standard computer software, namely TRNSYS and SUNCODE, have also been used to simulate the same building under similar conditions. Simulations have been performed for three different climatic zones in India for light and heavy constructions under conditions of glazed/unglazed areas and ventilation rates. The results are presented in terms of the hourly variation of the room temperature. For insulated heavy construction, the results of different models are significantly different. This difference is due to the use of different approaches to solve the heat conduction equations. SUNCODE depends on the RC network approach and underestimates the heat losses. TRNSYS uses the transfer function approach, which is sensitive to the initially assumed value of the room temperature. ADMIT represents a quasi-steady-state periodic variation and is not suitable for transient variations. For insulated light buildings, the heat transfer mechanisms used in the mathematical models are not the governing factors. The models also differ in treating the penetration of solar radiation through a glazed window and the subsequent heat-transfer mechanism. For a south window and air changes in an insulated building, the results obtained by SUNCODE and ADMIT are in good agreement, but the results obtained by TRNSYS are considerably different. The reason for this needs detailed analysis.     

Optical properties and laser performance of neodymium doped fluoroapatites SrxCa5−x(PO4)3F (x = 0, 1, 2, 3, 4, and 5)

Nd doped fluoroapatites Sr_xCa_5−x(PO₄)₃F(S_xC_5−xPF, X = 0, 1, 2, 3, 4, and 5) single crystals have been grown by the Czochralski technique. Their polarized absorption and emission spectra have been recorded at room temperature and used to calculate the absorption and stimulated emission cross sections. Broadening of the absorption and emission bands is observed for Nd³⁺ in the solid solutions SPF-CPF compared to Nd³⁺ in CPF or SPF. 1% Nd:S_xC_5−xPF, X = 0, 2, 3, 4, and 5, laser rods have been tested in a cavity longitudinally pumped by a 1 W AlGaAs laser diode and compared to Nd:YAG and Nd:YVO₄ rods. All fluoroapatites exhibit very good laser performance with low thresholds and high slope efficiencies, higher than in the case of YAG and equal to the YVO₄ samples. The dependance of the laser output power versus the diode temperature has also been measured for all materials. The laser output was found to be as sensitive to the diode temperature fluctuations for fluoroapatites as for YAG.     

The As-prepared surfaces of C-axis-oriented Nd1Ba2Cu3Oy thin films characterized using scanning probe microscopes

Recently, superconducting Nd₁Ba₂Cu₃O_y (Ndl23) thin films with high superconducting transition temperature (T _c) have been successfully fabricated at our institute employing the standard laser ablation method. In this paper, we report the results of surface characterization of the Nd123 thin films using an ultrahigh vacuum scanning tunneling microscope/spectroscopy (UHV-STM/STS) and an atomic force microscope (AFM) system operated in air. Clear spiral pattern is observed on the surfaces of Nd123 thin films by STM and AFM, suggesting that films are formed by two-dimensional island growth mode. Contour plots of the spirals show that the step heights of the spirals are not always the integer or half-integer number of thec-axis parameter of the structure. This implies that the surface natural termination layer of the films may not be unique. This result is supported byI-V STS measurements. The surface morphology of the Nd123 thin films is compared with that of thec-axis-oriented Y₁Ba₂Cu₃S_y thin films. Surface atomic images of the as-prepared Nd123 thin films are obtained employing both STM and AFM. STS measurements show that most of the surfaces are semiconductive. The results of STS measurements together with the fact that we are able to see the surface atomic images using scanning probe microscopes suggest that exposure to air does not cause serious degradation to the as-prepared surfaces of Nd123 thin films.     

Evaluation of in vitro stability of large unilamellar liposomes coated with a modified polysaccharide (O-palmitoylpullulan)

Aiming at encapsulation of a hydrosoluble drug, large unilamellar liposomes (LUV) of egg phosphatidylcholine (PC) were coated with a natural polysaccharide derivative, O-palmitoylpullulan (OPP), and its in vitro stability evaluated using fluorescent probes. This coating (in OPP/PC weight ratio of 3) improved significantly the in vitro stability of LUV by decreasing both the permeability and fluidity of the liposomal membrane.This paper was accepted for publication after the 1995 Conference of the European Society of Biomaterials, Oporto, Portugal, 10–13 September.