Substitution of an aspartic acid results in constitutive activation of c-kit receptor tyrosine kinase in a rat tumor mast cell line RBL-2H3

The c-kit protooncogene encodes a receptor tyrosine kinase that mediates signals required for differentiation, proliferation and survival of mast cells. We have already shown the constitutive activation of c-kit receptor tyrosine kinase (KIT) in a human mast cell leukemia line (HMC-1) and a murine mastocytoma cell line (P-815). We here examined whether such constitutive activation of KIT occurred in the rat tumor mast cell line RBL-2H3 as well, which is frequently used as a tool for studying functions of mast cells. In RBL-2H3 cells, KIT was constitutively phosphorylated on tyrosine and activated in the absence of autocrine production of its ligand, stem cell factor (SCF). Sequencing analysis revealed that one of c-kit genes of RBL-2H3 cells had a point mutation, resulting in amino acid substitution of Tyr for Asp in codon 817. When rat wild-type c-kit cDNA and mutant-type c-kit cDNA encoding KITTyr817 were transfected into cells of a human embryonic kidney cell line (293T), only mutant form KITTyr817 was constitutively phosphorylated on tyrosine and activated in the absence of SCF. Since mutations at the same Asp codon constitutively activated KIT in all the human HMC-1, murine P-815, and rat RBL-2H3 cell lines, and since the incorporation of antisense oligonucleotides of c-kit messenger RNA significantly suppressed the proliferation of RBL-2H3 cells, the activating mutations in the Asp codon of the c-kit gene appeared to be involved in neoplastic growth of mast cells.     

A 3-V, 2%-mW multibit current-mode ΣΔ DAC with 100 dBdynamic range

The area ratio of analog to digital for mixed-mode chip has been inversely proportional to the process design rule for a given dynamic range objective, in contradiction to the LSI trend. This paper presents a design approach to realize a high degree of size reduction with process design rules for analog circuitry and a signal processing architecture for digital circuitry. A five-level current-mode ΣΔ digital-to-analog converter (DAC) system reveals full scale total harmonic: distortion plus noise (THD+N) of -90 dB and dynamic-range of 100 dB at 3 V (low power of 22 mW). Analog-area down-scaling can be accomplished by this architecture to be 1.09 mm², using 0.6-μm double-poly double-metal (DPDM) CMOS. For the digital filter, a pipeline instruction sequence with multiplierless architecture also gives small area of 1.98 mm²     

Maturation of the posterolateral spinal fusion and its effect on load-sharing of spinal instrumentation. An in vivo sheep model

We investigated the temporal relationship among the biomechanical, radiographic, and histological properties of a posterolateral spinal fusion mass to elucidate the changes in load-sharing of the spinal instrumentation and that of the fusion mass throughout the healing process. Destabilization of the posterior spinal column and transpedicular screw fixation at the segments between the third and fourth and the fifth and sixth lumbar vertebrae was performed in twenty-four sheep. A posterolateral spinal arthrodesis with use of autologous corticocancellous bone graft was done randomly at one of the two segments; the other segment (without bone graft) served as the instrumented control. Six animals each were killed at four, eight, twelve, and sixteen weeks postoperatively. Biomechanical testing showed that the posterolateral fusion mass had increased mechanical stiffness after the fourth week. The strain on the hardware, measured with use of rods instrumented with strain-gauges, decreased significantly (p < 0.01) beginning at eight weeks. Radiographically, three independent observations of each of the six animals at each time-period showed that, although all of the fusion masses were considered solid unions at sixteen weeks, bridging of trabecular bone was noted during only ten of eighteen observations at twelve weeks, three of eighteen observations at eight weeks, and none of eighteen observations at four weeks. Computerized tomography and histomorphometric analyses demonstrated that mineralization in the fusion mass increased in a linear fashion even after eight weeks. Histologically, the fusion mass consisted predominantly of woven bone at eight weeks; thereafter, it was gradually trabeculated. CLINICAL RELEVANCE: We found a great discrepancy between biomechanical stability and histological maturation of the posterolateral fusion mass. The biomechanical properties of a stable spinal fusion preceded the radiographic appearance of a solid fusion by at least eight weeks, suggesting that immature woven bone provided substantial stiffness to the fusion mass. The spinal instrumentation was subjected predominantly to bending stress rather than to axial stress, and the load-sharing of the spinal instrumentation decreased concurrently with the development of the spinal fusion.     

Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-β can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.     

Correction to Kanayama et al. (2007).

Reports an error in "Testosterone supplementation for depressed men: Current research and suggested treatment guidelines" by Gen Kanayama, Revital Amiaz, Stuart Seidman and Harrison G. Pope Jr. (Experimental and Clinical Psychopharmacology, 2007[Dec], Vol 15[6], 529-538). In the "Recent Studies" section (pp. 531-532), citations to Pope and Katz (2003) should have been to Pope, Kanayama, Cohane, Siegel, and Hudson (2003) to reflect the following source, which was omitted from the reference list: "Pope, H. G., Jr., Kanayama, G., Cohane, G., Siegel, A., & Hudson, J. I. (2003). Testosterone gel supplementation for men with refractory depression: A randomized placebo-controlled trial. American Journal of Psychiatry, 160, 105-111". (The following abstract of the original article appeared in record 2007-18976-003.) Several lines of accumulating evidence suggest that testosterone might be effective for the treatment of depression, especially in older men who exhibit low testosterone levels. However, despite the potential promise of this approach, the available literature of controlled studies of testosterone in depression remains extremely limited. Therefore, testosterone treatment of depression must still be considered an experimental procedure. At the present state of research, it appears that testosterone might most likely show benefit as an augmentation strategy in men who exhibit low or borderline testosterone levels and who show only a partial response to conventional antidepressants. In this article, we provide some suggested practical guidelines for the treatment of such individuals. However, it should be recognized that these suggestions are tentative and will likely require revision as additional data become available. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhanced renal toxicity by inorganic mercury in metallothionein-null mice

To elucidate a protective role of metallothionein (MT) in the manifestation of inorganic mercury toxicity, we studied the susceptibility of MT-null mice to the renal toxicity of mercuric chloride. Because the MT-null (J) mice are a genetic background of 129/Sv strain, the 129/Sv mice were used as wild-type controls. Nine-week-old male MT-null (J) and 129/Sv mice were given subcutaneous injections of mercuric chloride at doses of 10 to 40 micromol/kg. The basal MT level in the kidney of MT-null (J) mice was undetectable (<0.2 microg/g of tissue) and approximately 2.5 microg/g of tissue in 129/Sv mice. The sensitivity to the renal toxicity of mercuric chloride was markedly enhanced in the MT-null (J) mice compared with the 129/Sv mice. The renal mercury level was similar for the MT-null (J) and 129/Sv mice at 4 hr after the injection of mercuric chloride (20 micromol/kg) but became significantly lower in MT-null (J) mice than in 129/Sv mice at 24 and 72 hr. Based on the present results, we conclude that MT is an important protective factor against the renal toxicity caused by inorganic mercury and that it may play a major role in the retention of mercury in the kidney.     

Preparation of new redox-active polyionenes with porphyrin units in the main chain

Quaternization of trans-dipyridylporphyrin with 1,4-butaneditrifluoromethane-sulfonate affords new polyionenes containing porphyrin units in the main chain. The polymers exhibit chemical and electrochemical reversible redox activities. Weitz-type two-step redox processes similar to those of viologens account for the redox properties of the polymers. Received: 26 November 1996/Revised: 24 January 1997/Accepted: 10 February 1997     

Boundary layer theory approach to the concentration layer adjacent to a ceiling wall of a hydrogen leakage: Far region

The field of the hydrogen leakage in partially open space can be divided into two main regions according to the importance of the hydrogen concentration distribution and the flow behavior. These two regions are the jet region and the boundary layer region which are adjacent to the ceiling wall of the space, resulting from impinging the hydrogen jet to the wall. The boundary layer region in turn can be divided into two regions, according to the modeling of the flow. These regions are the stagnation-point boundary layer region and the far boundary layer region. Previously, we studied the region of stagnation-point flow (Hiemenz flow) [El-Amin MF, Kanayama H. Boundary layer theory approach to the concentration layer adjacent to a ceiling wall at impinging region of a hydrogen leakage. Int J Hydrogen Energy, in press.]. The current paper is devoted to analyze the far region of the boundary layer adjacent to the ceiling wall using the boundary layer theory. Also, an experiment has been conducted on the hydrogen leakage in partially open space to estimate the concentration distribution vertically at the center of the domain under the ceiling wall. In order to verify the boundary layer theory approach, a comparison between the measurements and the boundary layer theory approximations is investigated and the results showed a good agreement. The wall shear stress, the local friction factor, the friction drag and the non-dimensional drag coefficient of the ceiling wall are calculated. Also, both momentum and concentration boundary layer thicknesses are estimated.     

Surface damage in ZrB2-based composite ceramics induced by electro-discharge machining

Electro-conductive ZrB₂-based composite ceramics, containing SiC and B₄C, were machined with an electro-discharge machining (EDM) process. The EDMed surfaces were covered with resolidified ZrB₂ layers. Many open pores and surface cracks were observed on the surfaces. The strength degradation of the ceramics caused by machining was evaluated by three point bending tests of the partially EDMed bending specimens. The effects of pulsed current, pulse duration and duty factor on the strength and the roughness of EDMed surfaces are discussed. The strength of EDMed specimens was increased with decreases in pulse current, pulse duration and duty factor. The roughness of EDMed surfaces was decreased with decreases in pulse current, pulse duration and duty factor. The reliability of the ceramics EDMed with the appropriate conditions was as high as that of the ceramics ground with a 400 grit diamond wheel. It would be possible to use the carefully EDMed ZrB₂-based composite ceramics as structural components without any additional finishing processes.