Src homology 2 protein tyrosine phosphatase (SHPTP2)/Src homology 2 phosphatase 2 (SHP2) tyrosine phosphatase is a positive regulator of the interleukin 5 receptor signal transduction pathways leading to the prolongation of eosinophil survival

Interleukin-5 (IL-5) regulates the growth and function of eosinophils. It induces rapid tyrosine phosphorylation of Lyn and Jak2 tyrosine kinases. The role of tyrosine phosphatases in IL-5 signal transduction has not been investigated. In this study, we provide first evidence that SH2 protein tyrosine phosphatase 2 (SHPTP2) phosphotyrosine phosphatase plays a key role in prevention of eosinophil death by IL-5. We found that IL-5 produced a rapid activation and tyrosine phosphorylation of SHPTP2 within 1 min. The tyrosine phosphorylated SHPTP2 was complexed with the adapter protein Grb2 in IL-5-stimulated eosinophils. Furthermore, SHPTP2 appeared to physically associate with beta common (betac) chain of the IL-5 receptor (IL-5betacR). The association of SHPTP2 with IL-5betacR was reconstituted using a synthetic phosphotyrosine-containing peptide, betac 605-624, encompassing tyrosine (Y)612. The binding to the phosphotyrosine-containing peptide increased the phosphatase activity of SHPTP2, whereas the same peptide with the phosphorylated Y612--> F mutation did not activate SHPTP2. Only SHPTP2 antisense oligonucleotides, but not sense SHPTP2, could inhibit tyrosine phosphorylation of microtubule-associated protein kinase, and reverse the eosinophil survival advantage provided by IL-5. Therefore, we conclude that the physical association of SHPTP2 with the phosphorylated betac receptor and Grb2 and its early activation are required for the coupling of the receptor to the Ras signaling pathway and for prevention of eosinophil death by IL-5.     

Expression studies of delta-globin gene alleles associated with reduced hemoglobin A2 levels in Greek Cypriots

We previously identified five delta-globin gene alleles associated with reduced hemoglobin (Hb) A2 (Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S. (1991) Blood 78, 3298-3305). We have now evaluated functional consequences of the changes after expression in COS-1 cells to monitor effects on RNA splicing. In addition, variant Hb A2 tetramers were expressed in yeast to assess effects of amino acid changes on oxygen binding and stability to heat and mechanical agitation. The G --> T change at codon 27 and the A --> G change in IVS-2 both affect RNA splicing, whereas the C --> T change at codon 97 and the AT deletion in IVS-2 have no effect. Oxygen equilibrium curves of the Hb A2 variants expressed in yeast were similar to that of wild type Hb A2. None of the three variant Hb A2 tetramers (Thr --> Ile at codon 4 (Hb deltaT4I), Ala --> Ser at codon 27 (Hb deltaA27S), and Arg --> Cys at codon 116 (Hb deltaR116C)) showed decreased heat stability compared with Hb A2, whereas the Hb deltaT4I variant showed highest instability to mechanical agitation. Co-expression in yeast of alpha-globin chain and the delta-chain variant containing a Leu --> Pro change at codon 141 yielded no identifiable tetramers, suggesting lack of assembly or severe tetramer instability. These studies show the probable cause for decreased Hb A2 for two alleles is due to defective splicing, whereas decreased protein stability, increased tetramer association with red cell membranes, increased interdisulfide bond formation of delta-chains, which inhibits assembly with alpha-chains, and/or reduced assembly is suggested for the other three alleles.     

Functioning survival rate of fixtures and superstructures of osseointegrated implants: ten years of progress in Tokyo Dental College Hospital (second report)

Endoglucanase production was measured in culture filtrates of four species of Saccobolus growing in media containing glucose or crystalline cellulose as the only carbon sources. Enzyme activity was four to seven times higher in the presence of cellulose than glucose. S. saccoboloides showed maximal growth and enzyme production. The extracellular proteins secreted during growth on cellulose were separated by polyacrylamide gel electrophoresis and stained for proteins. A zymogram technique was used to visualize bands with endoglucanase activity. The four species showed different protein and isoenzyme patterns.     

Annual changes in serum vitellogenin concentrations in viviparous eelpout, Zoarces elongatus

Vitellogenin of matrotrophic viviparous eelpout (Zoarces elongatus) was purified from estradiol-17 beta (E2) treated immature male sera by gel chromatography and anion exchange chromatography. Isolated vitellogenin has a molecular weight of 540 kDa estimated by gel chromatography. Serum levels of vitellogenin in females were measured during oocyte development and gestation by single radial immunodiffusion. Serum vitellogenin level was low (less than 0.2 mg/ml) during the early vitellogenic period, increased in the late vitellogenic period to a peak level (6.4 +/- 2.1 mg/ml) at the beginning of gestation. After that it rapidly decreased to a low level (0.1 +/- 0.1 mg/ml) during the early gestation period. Levels of vitellogenin remained low throughout the gestation period. Serum E2 levels in females showed increased from 1.3 to 3.0 ng/ml during the late vitellogenic period, and declined to 0.4 ng/ml during the early gestation period. Serum levels of E2 showed good correlation with serum vitellogenin levels, suggesting that the vitellogenin synthesis is controlled by E2 in this species. These results combined with the matrotrophic growth of embryo during gestation suggest that there is a shift in the synthesis of maternal nutritional products for embryos from the yolk to other nutrients.     

Stabilization of bioethanol recovery with silicone rubber‐coated ethanol‐permselective silicalite membranes by controlling the pH of acidic feed solution

In order to produce highly concentrated bioethanol by pervaporation using an ethanol‐permselective silicalite membrane, techniques to suppress adsorption of succinic acid, which is a chief by‐product of ethanol fermentation and causes the deterioration in pervaporation performance, onto the silicalite crystals was investigated. The amount adsorbed increased as the pH of the aqueous succinic acid solution decreased. The pervaporation performance also decreased with decreasing pH when the ternary mixtures of ethanol/water/succinic acid were separated. Using silicalite membranes individually coated with two types of silicone rubber, pervaporation performance was significantly improved in the pH range of 5 to 7, when compared with that of non‐coated silicalite membranes in ternary mixtures of ethanol/water/succinic acid. Moreover, when using a silicalite membrane double‐coated with the two types of silicone rubber, pervaporation performance was stabilized at lower pH values. In the separation of bioethanol by pervaporation using the double‐coated silicalite membrane, removal of accumulated substances having an ultraviolet absorption maximum at approximately 260 nm from the fermentation broth proved to be vital for efficient pervaporation. Copyright © 2005 Society of Chemical Industry     

Pressureless sintering and characterization of cordierite/ZrO2 composites

Cordierite/ZrO₂ composites with 5 to 25 wt% ZrO₂ were fabricated by conventional powder mixing and pressureless sintering method. Their densification behavior, microstructure, mechanical and thermal properties were studied. By dispersing 25 wt% (9.57 vol%) ZrO₂, densified cordierite/ZrO₂ composite with a relative density of 98.5% was obtained at an optimum sintering condition of 1440 °C and 2 h. ZrO₂ particles were homogenously dispersed within matrix grains and at the grain boundaries. The intragranular particles were finer than 100 nm and the intergranular particles were coarser. Both fracture strength and toughness could be enhanced more than two times higher, compare to those of monolithic cordierite, by dispersing 25 wt% ZrO₂ into the cordierite matrix. The toughening mechanism in the present composites was mainly attributed to martensitic transformation due to ZrO₂ dispersion. Electronic Publication     

A case report: multiple liver metastasis of gastric cancer responding to intraarterial infusion of MTX and 5-FU

In a 63-year-old male patient with gastric cancer having multiple liver metastases, the metastatic lesions responded well to postoperative staggered intraarterial infusion therapy with MTX and 5-FU. The intraarterial infusion therapy was administered once a week. A total of 5 courses of this therapy produced marked regression of liver metastases and remarkable necrosis. The effect was thus rated as PR. The patient is healthy and has been successfully rehabilitated. His dose is oral 5-FU (200 mg x 2).