Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats

Cerebral ischemia induces a massive efflux of glutamate causing delayed neuronal death in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). It is obvious that L-N-nitroarginine (L-NNA; NO synthase (NOS) inhibitor), benzamide (poly(ADP-ribose) synthetase inhibitor), and growth factors are involved in reducing neuronal cell death due to toxic conditions, especially phosphatidylinositol 3 (PI3)-kinase activity; however, no studies have clarified whether genetic vulnerability to neurotoxic states is present in cortical neurons isolated from SHRSP. For this purpose, we prepared cortical neurons from WKY and SHRSP (15 weeks of gestation) to test the genetic vulnerability involved in the pathogenesis of stroke as well as apoptosis of cortical neurons isolated from SHRSP. We also examined the mechanisms necessary to reduce apoptosis under neurotoxic states using ultrastructural and biochemical techniques. Cortical neurons from SHRSP were in fact found to be more vulnerable than neurons from WKY and resulted in apoptosis when treated with nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, especially insulin-like growth factor (IGF), rescued neurons from NO- and NMDA-mediated neurotoxicity, particularly those from SHRSP. Conversely, benzamide and L-NNA reduced NMDA-mediated neurotoxicity but not NO-mediated toxicity. The ability to protect neurons from neurotoxicity was as follows: IGF-->nerve growth factor epidermal growth factor-->L-NNA-->benzamide. In addition, it was demonstrated that wortmannin, a PI3-kinase inhibitor, lessened the protective effects of these growth factors against NO-mediated toxicity. The data thus indicate that genetic factors related to neuronal vulnerability to apoptosis are involved in the pathogenesis of stroke lesions in SHRSP. PI3-kinase activity, which is stimulated by growth factors, is closely related to protective effects against NO- and NMDA-mediated toxicity in cortical neurons, especially those isolated from SHRSP. Moreover, the genetic vulnerability observed in SHRSP neurons is possibly linked to the inadequate activation of signaling pathways in the downstream of protein tyrosine kinases.     

Shortening ratios of modified dipole antennas

Two types of modified dipole antennas, zigzag and meander-line types, are analyzed and the shortening ratios are calculated. A zigzag dipole antenna with a wire length of 0.58 wavelengths has a shortening ratio of 24 percent with a resonant resistance of46 Omega. A meander-line dipole antenna with a wire length of 0.70 wavelengths has a shortening ratio of 30 percent with a resonant resistance of43 Omega. It is found that the radiation patterns of these two types of antennas are similar to the radiation pattern of a conventional half-wave linear dipole antenna.     

External bit field analyses

Three-dimensional external bit fields emanating from single and multiple magnetic transitions with a finite track width have been calculated. The magnetic field interferences between tracks have been also simulated. The results show that the fields have a large component in the track width direction near the transition edges. This contributes to field extension in the neighboring track direction. The amount of extension decreases with bit density increase. The results of our calculations are backed up by Lorentz microscopy observation of films in which bit fields are transcribed.     

Evaluation of CVD/PVD multilayered seed for electrochemicaldeposition of Cu-damascene interconnects

Multilayered seed for electrochemical deposition (ECD) of Cu was investigated to develop narrow-pitched, dual-damascene Cu interconnects that will be required for future ULSI devices. The seed was obtained by the physical vapor deposition (PVD) of a Cu film followed by the chemical vapor deposition (CVD) of a Cu film. The seed of the thinner CVD-Cu element and the thicker PVD-Cu element demonstrated better filling characteristics in high-aspect ratio vias. Good current-voltage characteristics were demonstrated using the multilayered seed technique with Cu dual-damascene interconnects (0.28 μm minimum via size) resulting in a via resistance about 0.7 Ω. In addition, ring-oscillator circuits were fabricated by integrating the double-layered interconnects with a transistor having a 0.18 μm gate width. The propagation delay per inverter, which had an interconnect with 10⁴ vias, was about 6 ns. We successfully fabricated multilevel Cu-damascene interconnects, which are available for future high-speed devices using this multilayered seed technique     

Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features

The contiguous 874.423 base pair sequence corresponding to the 50.0-68.8 min region on the genetic map of the Escherichia coli K-12 (W3110) was constructed by the determination of DNA sequences in the 50.0-57.9 min region (360 kb) and two large (100 kb in all) and five short gaps in the 57.9-68.8 min region whose sequences had been registered in the DNA databases. We analyzed its sequence features and found that this region contained at least 894 potential open reading frames (ORFs), of which 346 (38.7%) were previously reported, 158 (17.7%) were homologous to other known genes, 232 (26.0%) were identical or similar to hypothetical genes registered in databases, and the remaining 158 (17.7%) showed no significant similarity to any other genes. A homology search of the ORFs also identified several new gene clusters. Those include two clusters of fimbrial genes, a gene cluster of three genes encoding homologues of the human long chain fatty acid degradation enzyme complex in the mitochondrial membrane, a cluster of at least nine genes involved in the utilization of ethanolamine, a cluster of the secondary set of 11 hyc genes participating in the formate hydrogenlyase reaction and a cluster of five genes coding for the homologues of degradation enzymes for aromatic hydrocarbons in Pseudomonas putida. We also noted a variety of novel genes, including two ORFs, which were homologous to the putative genes encoding xanthine dehydrogenase in the fly and a protein responsible for axonal guidance and outgrowth of the rat, mouse and nematode. An isoleucine tRNA gene, designated ileY, was also newly identified at 60.0 min.     

Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co-stimulatory molecules

After application of haptens to the skin, Langerhans cells (LC), i.e. immature dendritic cells (DC) in the skin, move to secondary lymphoid organs to sensitize naive T cells. During this process, LC become mature DC with augmented expression of various co-stimulatory molecules and MHC class II antigens. In this scenario, however, critical questions remain as to what kind of chemicals can induce this maturation process through what kind of mechanisms. To clarify these questions, we used monocyte-derived CD1a+ DC instead of LC since LC maturated spontaneously in vitro culture. After we confirmed that monocyte-derived DC showed at least phenotypic characteristics and a response to TNF-alpha similar to LC, we added various chemicals, i.e., dinitrochlorobenzene (DNCB), trinitrochlorobenzene (TNCB), NiCl2, ZnCl2, sodium dodecyl sulfate (SDS), or benzalkonium chloride (BC), to a culture of purified monocyte-derived CD1a+ DC. Of these chemicals, only NiCl2 and DNCB significantly increased the surface expression of CD54, CD86, HLA-DR antigen, and interleukin (IL)-1 beta production, while SDS, BC, or ZnCl2 could not augment them, except for weak augmentation of CD86 expression by SDS. The increase in the expression of CD86 induced by NiCl2 or DNCB was most remarkable, being observed in DC from almost all the subjects we examined. TNCB could also induce responses similar to those induced with DNCB, but the number of subjects whose DC responded to it was far less than that of subjects whose DC responded to NiCl2 or DNCB. In spite of the augmented CD86 expression on DC treated with DNCB or NiCl2, these chemicals induced different responses of DC in their expression of CD54 and HLA-DR and the production of IL-6 and tumor necrosis factor (TNF)-alpha. In addition, the up-regulation of CD86 expression on DC treated with DNCB was significantly suppressed by either anti-IL-1 beta or anti-TNF-alpha antibody, while that by NiCl2 was relatively insensitive to these antibody treatments. Finally, the protein kinase C inhibitor, H7, but not staurosporine, could suppress the augmentation of CD86 expression on DC induced either by NiCl2 or by DNCB. These data suggest that DC respond to some haptens by changing their expression of several co-stimulatory molecules and their production of cytokines with a resultant change in antigen-presenting function. They also suggest that these chemicals stimulate DC by different mechanisms. By these responses, DC may modulate the final immune response to chemicals.     

Turn-On and Turn-Off Characteristics of a 4.5-kV 3000-A Gate Turn-Off Thyristor

A 4.5-kV 3000-A gate turn-off (GTO) thyristor has been developed for use in high-power motor drive control equipment such as inverters and choppers. The high gate turn-off current of 3000 A is achieved by decreasing the variation of on-state voltages as well as turn-off times between segments which compose the GTO thyristor. This idea is supported by observation of infrared radiation during the turn-off process in the parallel operation of two segments with different on-state voltages or turn-off times. The parallel operation behavior is well simulated by a two-dimensional numerical simulation. Such design considerations and electrical characteristics of the newly developed high-power GTO thyristor are described. The device has a forward blocking capability of 4.5 kV, a maximum gate turn-off current of 3000 A, on-state voltage of 3.0 V at 3000 A, turn-on time of 10 ?s, and turn-off time of 25 ?s.     

Contact dermatitis of the ear due to a rubber earplug

A molecular analysis of the arylsulphatase A gene was performed on 26 unrelated, Italian, late infantile metachromatic leucodystrophy patients. The frequency of the common disease causing mutations 609A and 2381T was 28.8% and 1.9% respectively. Pseudodeficiency allele frequency in patients was found to be 13.5% and a frequency of 10.1% was found in 89 unaffected normal controls. The frequency of the 609A mutation in Italian late infantile patients is lower than in late infantile patients from northern Europe, suggesting a higher frequency of different sporadic mutations in the Italian population. A cooperative in cis effect in phenotype determination involving arylsulphatase A mutations and the eventual background of the pseudodeficiency allele is proposed.     

Effect of X-ray exposure on the pharmaceutical quality of drug tablets using X-ray inspection equipment

Context: X-ray inspection equipment is widely used to detect missing materials and defective goods in opaque containers. Its application has been expanded to the pharmaceutical industry to detect the presence of drug tablets in aluminum foil press-through packaging. However, the effect of X-rays on the pharmaceutical quality of drug tablets is not well known.

Objective: In this study, the effect of X-rays on the pharmaceutical quality of drug tablets was investigated.

Methods: Exposure of acetaminophen, loxoprofen and mefenamic acid tablets to X-ray doses of 0.34?mGy (thrice the dose by X-ray scanning) to 300?Gy (maximum dose from our X-ray equipment) was demonstrated, and the samples were evaluated by formulation tests.

Results: Exposure to X-rays did not affect the pharmaceutical quality of the drug content. The samples exposed to X-rays exhibited almost the same profile in formulation tests (dissolution test, disintegrating test and hardness test) as control samples (0?Gy). The combination of X-ray exposure with accelerated temperature and humidity tests (six months) also did not affect the pharmaceutical quality. The color change of light-sensitive drugs (nifedipine and furosemide tablets) after X-ray exposure was negligible (Conclusion: The X-ray scanning and X-ray exposure under our experimental conditions did not affect the pharmaceutical quality of drug tablets.