The functional role of CrkII in actin cytoskeleton organization and mitogenesis

Crk is a member of a family of adapter proteins predominantly composed of Src homology 2 and 3 domains, whose role in signaling pathways is presently unclear. Using an in situ electroporation system which permits the introduction of glutathione S-transferase (GST) fusion proteins into cells, we found that c-CrkII bound to p130(cas), but not to paxillin in serum-starved rat-1 fibroblasts overexpressing the human insulin receptor (HIRc cells) in vivo. 17 nM insulin stimulation dissociated the binding of c-CrkII to p130(cas), whereas 13 nM insulin-like growth factor-I, 16 nM epidermal growth factor (EGF), and 10% serum each showed little or no effect. We found that stress fiber formation is consistent with a change in the p130(cas).c-CrkII interactions before and after growth factor stimulation. Microinjection of either GST-Crk-SH2 or -Crk-(N)SH3 domains, or anti-Crk antibody each inhibited stress fiber formation before and after insulin-like growth factor-I, EGF, and serum stimulation. Insulin stimulation by itself caused stress fiber breakdown and there was no additive effect of microinjection. Microinjection of anti-p130(cas) antibody also blocked stress fiber formation in quiescent cells. Microinjection of the Crk-inhibitory reagents also inhibited DNA synthesis after insulin-like growth factor-I, EGF, and serum stimulation, but not after insulin. These data suggest that the complex containing p130(cas).c-CrkII may play a crucial role in actin cytoskeleton organization and in anchorage-dependent DNA synthesis.     

Hydrothermal Synthesis of Oriented Anatase Films Consisting of Columnar Aggregates and Their Wetting Properties

We hydrothermally synthesized anatase films on Ti substrates from transparent aqueous solutions of layered titanate colloids. The morphology and wetting properties of the films were examined. The films consisted of columnar aggregates grown on the Ti substrates, which resulted in high orientation. Randomly oriented films were obtained when alumina was used as a substrate, whereas the sol–gel precoating of a titanium oxide (TiO₂) layer on alumina substrates resulted in similar orientation as that of the films on Ti substrates. Thus, the presence of TiO₂ on the substrate surface plays an important role in the orientation of columnar aggregates. The columnar aggregates were similar in microstructure to the arms of a type of six-pointed star-like anatase aggregate synthesized hydrothermally from the same reaction solutions. They were composed of twins of tapered anatase nanocrystals, which provided a rough film surface. The film surface was highly hydrophilic and oleophilic due to the nanoscale roughness even when the film was not irradiated with UV light.     

A new method of accurate polarization measurement on isobaric analog resonance to detect parity non-conservation effect

For the study of parity mixing in the compound states, a method to measure the longitudinal analyzing power A_z of the isobaric analog resonance (IAR) as a function of energy in the proton elastic scattering is discussed. A thick target is used and energy loss of the protons in the target is utilized to measure the energy dependence. The energy resolution is presented and the sources of the systematic errors in A_z are discussed together with the way of their elimination. The method has been shown to be quite efficient for deriving both the transverse and the longitudinal analyzing powers. The measurement of A_z for the s-wave IAR at E_cm=5.86 MeV in ⁹⁰Zr(p,p) and the analysis to derive PNC matrix elements are described.     

Supercritical CO2 extraction of pigment components with pharmaceutical importance from Chlorella vulgaris

BACKGROUND: Chlorella vulgaris is a green microalgae that contains various pigment components of carotenoids and chlorophylls. Supercritical CO₂ is widely used for extraction of pharmaceutical compounds because it is non‐oxic and easily separated from extracted material by simply depressurizing. In this work, pharmaceutical compounds from Chlorella vulgaris have been extracted using supercritical CO₂ with or without entrainer at various extraction conditions. RESULTS: Based on high performance liquid chromatography (HPLC) analysis, the extracts contained pigment components, such as lutein, β‐carotene, chlorophyll a and b. Higher extraction pressure and temperature promoted higher lutein extraction by supercritical CO₂. The optimum pressure and temperature for extraction were obtained as 50 MPa and 80 °C. Ethanol as an entrainer was more effective than acetone for the extraction of pigment components. Pigment components in the extract obtained by supercritical CO₂ with and without entrainer were compared with the extract obtained by a conventional extraction method. CONCLUSION: Supercritical CO₂ has been successfully applied for the extraction of pigment components from Chlorella vulgaris. Supercritical CO₂ enabled high selectivity for lutein extraction; however, the lutein yield was lower than that obtained by extraction using supercritical CO₂ with ethanol and soxhlet. Copyright © 2008 Society of Chemical Industry     

Safety and pharmacokinetics of CS-834, a new oral carbapenem antibiotic, in healthy volunteers

CS-834, (+)-[pivaloyloxymethyl (4R,5S,6S)-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(R)-5-oxopyrroli din-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate], is an ester-type oral carbapenem prodrug, and an active metabolite is R-95867, which has antibacterial activity. CS-834 was administered orally to healthy male volunteers at single doses of 50, 100, 200, and 400 mg and at a multiple dose of 150 mg three times a day for 7 days to investigate its safety and pharmacokinetic profiles. Other studies were conducted to examine the effect of food intake on the bioavailability of CS-834 and also the effect of the coadministration of probenecid on the pharmacokinetics of CS-834. In the fasting state, the concentration of R-95867 in plasma reached maximum levels from 1.1 to 1.7 h after the oral administration of CS-834, followed by a monoexponential decrease. The maximum concentrations of R-95867 in serum (C[max]s) after the administration of CS-834 at doses of 50, 100, 200, and 400 mg were 0.51, 0.97, 1.59, and 2.51 microg/ml, respectively. The half-lives (t1/2s) were almost constant, approximately 0.7 h. The areas under the concentration-time curves (AUCs) were proportional to the doses, ranging from 50 to 400 mg x h/ml. The cumulative recoveries in urine were approximately 30 to 35% until 24 h after drug administration. The C(max), AUC, t1/2, and recovery in urine were not affected by food intake. Probenecid coadministration prolonged the t1/2, and it increased the C(max) and AUC for R-95867 by approximately 1.5- and 2.1-fold, respectively. The multiple-dose study showed no change in the pharmacokinetics from those for the single doses and no drug accumulation in the body. A mild transient soft stool was observed in one volunteer in the study with a single dose of 400 mg. In the multiple-dose study, mild transient soft stools were observed in six volunteers, one volunteer had mild transient diarrhea, and one volunteer had elevated serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase levels (1.4- and 2.8-fold compared with the upper limits of normal, respectively). There were no other abnormal findings for objective symptoms or laboratory findings, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, blood chemistry, and urinalysis.     

Salivary duct carcinoma: a clinicopathologic study of three cases with a review of the literature

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located in the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intraductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comedolike necrosis was observed. Immunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S-100 protein, alpha-smooth muscle actin or muscle specific actin. Ultrastructurally, intracytoplasmic lumina with microvilli, a moderate number of mitochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of the patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be differentiated from low-grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.     

Abdominal incisional hernia occurring after an esophagectomy reconstructed with a gastric tube through an antesternal route: report of a case

A Japanese man, who had undergone a subtotal esophagectomy reconstructed with a gastric tube through an antesternal route for esophageal carcinoma 16 years previously, was admitted to our hospital because of an abdominal incisional hernia. The abdominal incisional hernia was in his upper abdomen and was difficult to push back into the intraabdominal cavity by hand. The hernia was successfully repaired by operation. We thus conclude that an abdominal incisional hernia is a rare but important late-phase complication occurring after an esophagectomy reconstructed with either an antesternal or retrosternal route, and an operation should be the treatment of choice.     

A METHOD FOR THE PREPARATION OF RAW POWDER FOR THE TANTALUM CAPACITOR: INFLUENCE OF PARTICLE SIZE AND BINDER CONTENT

Raw powder for use in the tantalum solid electrolytic capacitor was prepared by different processes, that is, the wet method (currently used conversion method) and the dry method (the proposed method). The properties of prepared powder from the dry method were compared with those of the wet method. The present report has focused on the relationship between the conditions of binder preparation and the properties of the prepared powder, such as the particle size distribution, angle of repose, and the tap density, respectively. Furthermore, the utility of the dry method was investigated.

Based on the results, it has been clarified that the properties of powder prepared by the dry method differ from those of the wet method. In the case of the dry method, it is suggested that the mechanism of preparation of the fine binder (PMMA powder) differs from that of the coarse binder. Furthermore, based on the experimental results, it has been suggested that the dry method could be used as the preparation method of the raw powder used in the tantalum solid electrolytic capacitor.     

Interaction and orientation of an alpha-aminoisobutyric acid- and tryptophan-containing short helical peptide pore-former in phospholipid vesicles, as revealed by fluorescence spectroscopy

The interaction and orientation of a membrane protein ion channel model, an alpha-aminoisobutyric acid analogue of gramicidin B (GBA), in egg yolk phosphatidylcholine vesicles was studied by means of fluorescence spectroscopic techniques. GBA helices form stable ion-conducting pores in membranes [Jelokhani-Niaraki et al. (1995) J. Chem. Soc. Perkin Trans. 2, 801-808]. In an alpha-helical model for the peptide, all Trp residues (intrinsic fluorophores) are distributed near the C-terminus. Fluorescence quenching experiments revealed the exposure of the helical peptides' C-termini to aqueous environments. Dansyl-labeled vesicles were used to investigate the GBA dynamism of the interaction with membranes. It was shown that considerable amounts of peptide reside on and in the vicinity of the outer surface of lipid bilayers. The transmembrane transfer to the inner layer is slow due to the high affinity of Trp residues for bilayer interfaces which anchor the peptide to the outer surface. A structural-functional interpretation of the GBA interaction with membranes is presented.     

Electrical properties of nickel in silicon

Electrical activity and energy levels as well as diffusion properties of nickel in silicon have not yet been reliably established. In this paper, we investigated the diffusion and the electrical properties of nickel in silicon to confirm that nickel is electrically active and introduces one acceptor and one donor level by combined measurements of Hall coefficient and DLTS, and measurements of the distribution of electrically active nickel in various silicon diodes by DLTS. The former experiments show that bothn- andp- type silicon are compensated by nickel and that nickel introduces an acceptor level ofE _c-0.47 ± 0.04 eV and a donor level ofE _v +0.18 ± 0.02 eV. The concentrations of these two levels are almost identical over the diffusion temperatures from about 800 to 1100° C, indicating that these donor and acceptor levels are due to different charge states of the same nickel center. In the distribution measurements of electrically active nickel in silicon diodes, we inspected how nickel can be observed by DLTS. It was found that the nickel diffusion intop- n junction is rather complicated, the distribution profiles of nickel in the vicinity of thep- n junction being markedly influenced by an additional heating at elevated temperatures after the nickel diffusion. This gives evidence that the difference in silicon devices used in various studies could give rise to different results.