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Promyelocytic leukemia (PML) bodies are discrete nuclear foci that are intimately associated with many DNA viruses. In human cytomegalovirus (HCMV) infection, the IE1 (for “immediate-early 1”) protein has a marked effect on PML bodies via de-SUMOylation of PML protein. Here, we report a novel real-time monitoring system for HCMV-infected cells using a newly established cell line (SE/15) that stably expresses green fluorescent protein (GFP)-PML protein. In SE/15 cells, HCMV infection causes specific and efficient dispersion of GFP-PML bodies in an IE1-dependent manner, allowing the infected cells to be monitored by fluorescence microscopy without immunostaining. Since a specific change in the detergent solubility of GFP-PML occurs upon infection, the infected cells can be quantified by GFP fluorescence measurement after extraction. With this assay, the inhibitory effects of heparin and neutralizing antibodies were determined in small-scale cultures, indicating its usefulness for screening inhibitory reagents for laboratory virus strains. Furthermore, we established a sensitive imaging assay by counting the number of nuclei containing dispersed GFP-PML, which is applicable for titration of slow-growing clinical isolates. In all strains tested, the virus titers estimated by the GFP-PML imaging assay were well correlated with the plaque-forming cell numbers determined in human embryonic lung cells. Coculture of SE/15 cells and HCMV-infected fibroblasts permitted a rapid and reliable method for estimating the 50% inhibitory concentration values of drugs for clinical isolates in susceptibility testing. Taken together, these results demonstrate the development of a rapid, sensitive, quantitative, and specific detection system for HCMV-infected cells involving a simple procedure that can be used for titration of low-titer clinical isolates.

The author’s recent studies on the critical current properties in Bi-2223 multifilamentary tapes as well as YBCO coated IBAD tapes have been reviewed. Extended electric field vs. current density ( E – J ) characteristics were studied over wide range of temperature, T , magnetic field, B , and angle, θ . Based on the analysis of statistic J c distribution and scaling, we derived an analytical expression for J as a function of E , T , B , and θ . This method allows us to describe and extrapolate the nonlinear E – J characteristics even in extremely low E region and/or high B region based on rather simple measurements.

We assessed the requirement of the host cytoskeleton for the intracytosolic transport of incoming human cytomegalovirus (HCMV) capsids. Treatments with microtubule (MT)-depolymerizing drugs nocodazole and colchicine led to a drastic decrease in levels of IE1 antigen, whereas cytochalasin B had no effect on the level of IE1 as determined by Western blot analyses. Sequential treatment including nocodazole washout and removal of cell surface virion revealed that HCMV entry into the cells occurred normally in the absence of the MT network. This finding was also supported by data obtained by monitoring pUL83 signals with an immunofluorescent assay (IFA). Furthermore, we demonstrated a close association of incoming HCMV capsids with MTs by IFA and ultrastructural analyses. In the absence of the MT network, the capsids which had entered the cytoplasm did not move to close proximity of the nucleus. These data suggest that HCMV capsids associate with the MT network to facilitate their own movement to the nucleus before the onset of immediate-early (IE) gene expression and that this association is required to start efficient IE gene expression.

Hip dislocations remain an intractable problem in patients with soft tissue impairment, particularly in those with muscle weakness around the hip, such as those who have undergone revision total hip arthroplasty (THA). At the authors' hospital, postoperative dislocations were observed in 10 of 154 hips between January 1985 and June 1988. Five hips required re-replacement. Conventional measures to prevent or treat post-THA dislocations have been anti-dislocation pants for soft fixation and a cast or abduction-forcing braces for firm fixation. However, the anti-dislocation pants for soft fixation were not as effective as indicated by the above 10 postoperative dislocations. The firm fixation techniques are considered to cause a reduction in muscle strength, causing psychological stress and poor activity of daily living (ADL). The authors devised a soft brace for easy application and prepared its test model to prevent muscle weakening, allow stability of the hip during rotation and avoid restrictions in ADL. This brace was applied to a patient who had 3 dislocations in a short period after being discharged who sustained a postoperative dislocation and achieved good results.

We have used a virus overlay assay to detect cellular proteins associated with human cytomegalovirus (HCMV) particles. The radiolabeled HCMV particles specifically bound to two host proteins with molecular sizes of 150 and 180 kDa. By a micro-amino-acid sequencing technique, the 180-kDa protein was identified as a human homologue of the ES130/p180 ribosome receptor (p180), which is an integral endoplasmic reticulum (ER) membrane protein possessing a very unique tandem repeat domain at its N-terminal region. The virus overlay assay using truncated p180 polypeptides revealed that HCMV binding to human p180 occurred through the N-terminal region. In HCMV-permissive cells the high level of expression of the human p180 protein was clearly observed regardless of cell type. Furthermore, we showed that p180 binds to the UL48 gene product, which is one of the predominant tegument proteins of HCMV and which is considered to be tightly associated with the capsid. The interaction between the two proteins was assumed to be specific and was observed both in vitro and in vivo. During the late phase of infection, the unique relocation of human p180 was observed, that is, to the juxtanuclear region, which appeared to be in the vicinity of the area where naked virions were frequently observed in an electron-microscopic study. Thus our data suggest that p180 interacts with the HCMV tegument, at least through pUL48, during the HCMV replication process. We discuss the possible role of the interaction between p180 and pUL48 in the intracellular transport of HCMV virions.

Background: S-mephenytoin 4’-hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19-related genetic polymorphism. Aim: To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status. Methods: Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post-dose. Results: Five homo EM, six hetero EM and four PM subjects were H. pylori-negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC0–24 and plasma levels of rabeprazole were observed among the three different genotype groups. Conclusion: The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.

It has been reported that most children who showed anaphylaxis to measles, mumps and rubella vaccines containing bovine gelatin as a stabilizer have anti-bovine gelatin IgE. The present study was designed to investigate the reactivity of IgE in bovine gelatin-sensitive children to gelatins from various animals, and the antigenic cross-reactivity between the gelatins. Serum samples taken from 10 children who showed anaphylaxis to vaccines containing bovine gelatin were used in this study. The level of anti-bovine gelatin IgE in these serum samples ranged from 11.0 to 251 Ua/ml. The IgE in most of the children reacted to kangaroo and mouse gelatins, to which they had had little or no exposure as a food or a vaccine stabilizer. The IgE binding to kangaroo and mouse gelatins was completely inhibited by bovine gelatin, whereas reciprocal inhibition was not complete, indicating that antigenic cross-reactivity is present between the mammalian gelatins. Only one child had strong IgE reactivity to fish gelatins, and this reactivity was not inhibited by bovine gelatin, indicating that no antigenic cross-reactivity exists between bovine and fish gelatins. Most of the children who displayed sensitivity to bovine gelatin showed IgE reactivity to other mammalian gelatins. This reactivity may be due primarily to the antigenic cross-reactivity between mammalian gelatins.

Interactions between human cytomegalovirus (HCMV) and various carbohydrate structures were analysed using sulfated glucuronyl glycosphingolipids (SGGLs) and the structurally related glycosphingolipids (GLs). A thin-layer chromatography-overlay assay and a solid-phase binding assay revealed that HCMV strongly bound to sulfated glucuronyl lactosaminylparagloboside, one of the SGGLs having the repeating lactosamine structure (3Gal beta1-4GlcNAc1-)2 in addition to the 3-O-sulfated glucuronyl moiety. The virus bound less strongly to other 3-O-sulfated GLs, which included sulfated glucuronyl paragloboside and cerebroside sulfate ester, and also to (3Gal beta1-4GlcNAc1-)2-containing GLs that included nLc6Cer. Thus, a (3Gal beta1-4GlcNAc1-)2 and a 3-O-sulfated saccharide seem to be important structures for the binding by HCMV. When virus particles were preincubated with these GLs, inhibitory effects were observed both on expression of the viral immediate-early gene and on plaque formation by HCMV. These effects were very well correlated with the abilities of the GLs to bind to the virus. Pretreatment of host cells with HNK-1 monoclonal antibody, which specifically recognizes SGGLs, resulted in partial inhibition of plaque formation by HCMV. These results clearly show that HCMV recognizes and binds to the sulfated carbohydrate structure in SGGL and also suggest that binding of HCMV to the specific sugar structure may play an important role in HCMV infection.

The first case of human systemic infection by an Aspergillus flavus isolate demonstrated to produce aflatoxins in vitro and in vivo is described. The patient, a 41-year-old man with acute myelogenous leukaemia, developed a complication of suspected pulmonary Aspergillus infection during remission induction therapy. Antifungal chemotherapy brought about a considerable degree of improvement, but remission of the underlying disease was not attained. Bone marrow transplantation was also not effective. The patient showed recovery from neutropenia but died despite aggressive antifungal chemotherapy. The autopsy revealed lesions in the lungs, myocardium, kidneys, brain, thyroid gland and skin due to a suspected Aspergillus sp. A fungus isolated from the right lung and the skin lesions was identified as A. flavus. Aflatoxins B1, B2 and M1 were detected in culture filtrates of the isolated A. flavus, and in an extract of lung lesions. These aflatoxins are considered to have played an important role in damaging the immune system of the patient through their toxic effects.

The demand for energy in Japan is expected to increase steadily into the future, and it seems that the importance of nuclear power generation will be heightened more when the situation of our country which is not rich in energy resources is taken into account. Furthermore, when we consider the present situation that the light water reactors have become common, recent outlook for the supply and demand for uranium resources, trends in the development of the fast breeder reactor technology, etc., the light water reactors are expected to remain dominant in the nuclear power generation of our country until at least the second half of the 21st century. Based on such a background five PWR utilities in Japan (Hokkaido, Kansai, Shikoku, Kyushu, and the Japan Atomic Power), and Mitsubishi Heavy Industries, Ltd. have jointly started researching the Next Generation PWR which is expected to be the leading nuclear power plant taking place of APWR.

The extraction of rare earth metals with liquid surfactant membranes, which contained 2-ethylhexyl-mono-2-ethylhexylphosphonic acid (PC-88A) as a carrier and sorbitan monooleate (Span 80) or L -glutamic acid dioleyl ester quaternary ammonium chloride as a surfactant, was conducted in a Mixco extractor. The concentration profile of rare earth metals along the column was measured. The experimental results were analysed by the backflow model taking into account the interfacial reaction between rare earth metals in the continuous aqueous phase and the carriers in the liquid membrane phase. The concentration profile for each of the two rare earth metals (La, Y) in a dual-component solution along the column was successively simulated by using the interfacial reaction rate constants obtained in previous batchwise experiments.

We examined serum anti-cytomegalovirus (CMV) and anti-ganglioside antibodies by ELISA in 51 patients with Guillain-Barré syndrome (GBS), and titers were compared with those from 47 normal and 74 disease controls. Three GBS patients with IgM anti-CMV antibodies had high titers of IgM and IgG anti-GM2 antibodies. The other GBS patients without IgM anti-CMV antibodies, and the normal and disease controls except one of 6 non-GBS patients with acute CMV infections had no anti-GM2 antibodies. The titers of anti-GM2 antibodies decreased on absorption with CMV-infected cells. These findings suggest that anti-GM2 antibodies are associated with acute CMV infections in GBS patients.

Electron density distributions ρ(r) contain three types of features, which give rise to a new natural approach of analyzing ρ with respect to chemical bonding. These features are 1) the very large spherical atomic core densities, defining the geometric structure, 2) the small multipolar atomic valence densities, defining the orientation and population of partially filled p- and d-shells of the “independent atoms” in the molecule or crystal, and 3) the very small density deformations due to the interatomic interactions. The valence shell parameters and the Chemical Deformation Densities are determined theoretically and experimentally for molecules and crystals. The features are brought in relation to intramolecular and intramolecular interactions.

The authors describe the results of an accelerated water treeing test after a period of approximately one year with two recently manufactured (1988) varieties of commercial EPR (ethylene-propylene rubber) cables, produced by different manufacturers and possessing different cable structures, as well as water impervious XLPE cable for comparison. In the test, bow-tie trees were found in the EPR insulation, which had previously been thought to develop no or few bow-tie trees. The analysis results of bow-tie in EPR cables are described. >

Some studies have demonstrated the benefit of blood glucose control as close as possible to physiological conditions. Not enough reports have investigated in detail the 24-h plasma profiles of insulin/glucose/C-peptide. Here we investigated the 24-h plasma profiles of physiological insulin/glucose/C-peptide in healthy Japanese adults.In order to evaluate the 24-h profiles of physiological insulin/glucose/C-peptide profiles, 42 blood samples were taken from each subject in our group of healthy Japanese volunteers to measure the 24-h profile with three standardized meals.Plasma glucose and insulin increased rapidly followed by a rapid decrease after each meal with little variation at night. The average peak values of insulin after each meal were as follows: 426.20 pmol/L (breakfast), 373.75 pmol/L (lunch), and 410.28 pmol/L (dinner). The average times to peak insulin were 0.651 h (breakfast), 0.677 h (lunch), and 0.689 h (dinner). The corresponding average maximum postprandial plasma glucose levels were 8.39 mmol/L (breakfast), 8.77 mmol/L (lunch), and 8.74 mmol/L (dinner). The average times to peak glucose were 0.738 h (breakfast), 0.650 h (lunch), and 0.625 h (dinner). The average maximum postprandial C-peptide levels were 2.64 nmol/L (breakfast), 2.55 nmol/L (lunch), and 2.67 nmol/L (dinner). No major differences were found in these parameters between the Caucasian and Japanese populations.This is the first investigation to measure the 24-h profiles of insulin/glucose/C-peptide in healthy Japanese volunteers with standardized meals. It is hoped this information will provide useful reference for future research and clinical management.

Human papillomavirus (HPV) E6 and E7 gene products play a central role in the induction of benign proliferation and malignant transformation by interacting with several cellular regulatory proteins such as p53, p16(INK4a), and nuclear factor kappaB (NF-kappaB). In this study, HPV DNA was detected by in situ hybridization (ISH) and p53, p16(INK4a), and NF-kappaB by immunochemistry in 22 penile cancer cases in Kenya. HPV DNA was found in 68.2% of the cases. There was no difference in the p53- and p16(INK4a)-positivities in HPV DNA-positive and HPV DNA-negative cases. In HPV DNA-positive cases, the NF-kappaB positivity in the nucleus, cytoplasm, and nucleus and/or cytoplasm amounted to 73.3%, 93.3%, and 100%, respectively, while in HPV DNA-negative cases, a 28.7% NF-kappaB positivity of in the nucleus and/or cytoplasm was observed. It is concluded that NF-kappaB in penile cancer is expressed more frequently in the presence of HPV infection than in its absence.

Poly(dimethylsiloxane)s (PDMS) of molecular weight, M w , = 8 × 10 4 −1.15 × 10 6 were found to be partially miscible with poly(methylethylsiloxane)s (PMES) of M w = 4 × 10 3 −9 × 10 3 , exhibiting the upper critical solution temperature. The extremum temperature, T cl,ex , of the cloud-point curve ranged from room temperature to 100°C, and the T cl,ex of ternary blends consisting of PDMS and PMES having a bimodal molecular weight distribution could be controlled by changing the composition of the low and high molecular weight fractions in PMES. The temperature dependence of the interaction parameter χ between PDMS and PMES could be reasonably determined from the molecular weight dependence of T cl,ex . The result is expressed as χ ( per PMES monomer unit ) = 4.07 T( K ) − 2.00 × 10 −3 , showing that the enthalpy term in χ is dominant. For a particular mixture with very narrow molecular weight distributions, the critical point was determined by measuring the volume ratio of two demixed phases and was found to shift from the extremum of the cloud point curve, indicating that the location of the critical point is very sensitive to the polydispersity.

Objectives Liraglutide is a once-daily human GLP-1 analog being developed as a Type 2 diabetes therapy. A dose-finding study in Japanese patients with Type 2 diabetes showed liraglutide to produce dose-dependent decreases in HbA(1C). Studies have also shown that, with stepped dose titration, liraglutide is well tolerated. This double-blind trial in 24 healthy Japanese men assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of once-daily subcutaneous (s.c.) liraglutide using doses exceeding those previously studied, and using the stepped titration approach. Materials and methods Subjects were randomized to three groups in each of which 6 received liraglutide, and 2 placebo for 35 consecutive days. The daily dose of liraglutide was stepped from 5 microg/kg (s.c. abdomen, morning) to 10 and then 15 microg/kg at 7-day intervals. One group remained at this dose, the others titrating further to 20 and 25 microg/kg, respectively. Subjects remained at the study site from Day 21 until the end of the trial, with standard meals served during inhouse periods. Results No safety issues, hypoglycemia, gastrointestinal or any other adverse events were observed. Liraglutide showed dose-dependent increases in the pharmacokinetic parameters of AUC0-24 h, C(max) and C(trough), while t(max), t(1/2) and V(d/F) were constant. Mean plasma glucose concentrations were similar across all treatment groups at baseline, but dose-dependent decreases in mean and postprandial plasma glucose were seen with liraglutide, although all values remained within normal ranges. There was a tendency for weight to decrease with liraglutide in comparison to placebo. Conclusions Liraglutide appears to be well tolerated at doses of up to 25 microg/kg in Japanese subjects. Despite clear pharmacodynamic effects in this euglycemic cohort, a low risk for hypoglycemia was suggested together with good gastrointestinal tolerability.

In the present paper, we examine the development of a high-quality acoustics system called the sound field generation system (SFGS) using a power envelope inverse filtering (PEIF) proposed by the authors. PEIF is used for preprocessing of the SFGS, and we quantitatively evaluate SFGS using a real signal. When the output signal of SFGS is reproduced in the reproduction field, the effect of the SFGS is diminished due to the impulse response of reproduction field that is added to the created SFGS signal. Therefore, we attempted to reduce the influence of the reproduction field using a PEIF. In the experiment, we used five signals, namely, male speech, female speech, male vocal with music, female vocal with music, and classical music, and these signals were processed by computer simulation. We evaluated these signals by objective evaluation and subjective evaluation. In the objective evaluation, we obtained an improvement in SFGS for the results ranging from approximately 1 dB to 2 dB under 4 kHz, and up to 5 dB above 4 kHz. In the subjective evaluation, we obtained an improvement of approximately 10% to 60% in an experiment involving 52 subjects. These improvements are significant.

On-core water impervious power cable has a water-impervious layer consisting of lead foil and a semiconducting plastic film. This layer is thermally bounded to the insulation shield of the cable core and prevents ingress of water to its interior. According to this design, the water-impervious layer is subjected to thermal expansion and contraction directly from the core and, as a result, thermal fatigue properties assume greater importance. Factors such as strain in the water-impervious layer, aging behavior of the lead foil, heat cycle behavior on the cable, and high-temperature behavior of composite tapes were investigated. Based on these results, it is estimated that the life of the on-core water-impervious layer is approximately 40 yrs. >

A 50-year-old man was admitted suffering from severe anemia and renal dysfunction. He had been admitted for the first time at the age of 49, and was diagnosed with multicentric Castleman's disease (MCD) and secondary amyloidosis. At that time, marked erythroid hypoplasia was demonstrated by both aspiration and biopsy of bone marrow. A diagnosis of pure red-cell aplasia (PRCA) was made. Immunosuppressive agents improved his symptoms and laboratory data. We report here a very rare case of PRCA following MCD and amyloidosis, and with reference to the literature, we discuss the relation between MCD and related diseases.

A novel resist pattern transfer process for the 70 nm technology node is presented using 157-nm lithography. By using newly developed 157-nm resists and a 157-nm microstepper (NA=0.60), sub-100 nm resist patterns are fabricated. Three types of structures are presented for the pattern transfer process. Two of these are hard mask (HM) processes. and the other is a bi-layer process using Si-containing resist. For all these structures, the underlayers of resist work well as anti-reflecting layers. By optimizing the RIE gas conditions, resist patterns are successfully transferred to the underlayer. Using the HM as an etching mask, sub-100 nm gate patterns are fabricated.

The authors review the effects of thermal expansion and contraction of the cable core on the service life of lead used as the water-impervious layer of XLPE (cross-linked polyethylene), and examine the relationship between the lead alloy composition of the water-impervious layer and the load cycle property of water-impervious cable in emergency operation. It is shown that the lead alloy composition used as the water-impervious layer plays an important role in the thermal fatigue property. >

Advantage of MOSFET SPICE parameter prediction by combining TCAD and BSIM3 model is presented. This method can release sufficient SPICE parameters without wafer fabrication. Lithography TCAD can reduce pattern optimization work. Device development time reduction is also presented with fabricated SRAM results.

We report a 78-year-old man with Guillain-Barré syndrome (GBS) who showed upper limb dominant muscle weakness following an upper respiratory infection. He had no weakness in extraocular, oropharyngeal and neck muscles. Tendon reflexes were absent in his upper limbs. Electrophysiological studies suggested demyelination of motor nerves in his upper and lower extremities. He had serum IgG antibodies to GM1 and GT1a but not to GQ1b. Anti-GT1a antibodies did not cross-react to GM1 by means of the absorption test. Titers of the antibodies decreased after recovering from muscle weakness of upper limbs. Since the presence of serum antibodies to GT1a but not to GQ1b were reported in patients with pharyngeal-cervical-brachial weakness of Guillain-Barré syndrome, it has been suggested that anti-GT1a antibodies play a role in acute oropharyngeal neuropathy. This is the first report of a patient with GBS lacking oropharyngeal palsy who had serum IgG antibodies to GT1a but not to GQ1b. Our case suggests that anti-GT1a antibodies are related not only with acute oropharyngeal neuropathy but also with upper limb dominant motor neuropathy.

Fas-associated phosphatase-1 (FAP-1) has been reported as a negative regulator of Fas-mediated signal transduction in human cancer cells. To obtain insights into the potential carcinogenesis of the FAP-1 gene, we investigated its transcriptional regulation in normal and cancerous cells. To identify the FAP-1 promoter sequences, we first isolated P1 and cosmid clones that contained the regulatory region upstream from the FAP-1 gene by using the PCR products of 5' rapid amplification of cDNA end (5'-RACE) as probes. Genomic analysis of positive clones revealed that the major FAP-1 mRNA was transcribed from its proximal promoter (pPRM) in all human cancer cell lines tested, but 1 additional large transcript derived from its distal promoter (dPRM) was found in the human colon cancer cell line DLD-1. This suggests that the FAP-1 gene may be aberrantly dysregulated in some types of human cancers, including colon carcinoma. Sequence analysis of the region upstream from the FAP-1 gene strongly suggests that the transcript of the FAP-1 gene may be controlled by a variety of transcriptional regulatory elements, including NF-kappa B, NF-IL6, and p53 in its 2 promoters. These results imply that the FAP-1 gene may be a target gene under the control of important apoptosis-related nuclear factors in human cancers.

It has been reported that the disaccharide composition of dermatan sulphate shows transient changes after epicutaneous application of the hapten 2,4-dinitrofluorobenzene to mouse skin, and that these changes are most conspicuous in healing skin on day 15 after chemical insult [Kuwaba, Nomura, Irie and Koyama (1999) J. Dermatol. Sci. 19, 23-30]. In the present study it was found that the molecular size of dermatan sulphate was increased on day 15 after hapten application. The molecular size of decorin increased in healing skin, whereas the size of dermatan-sulphate-depleted core protein did not increase. The length and localization of decorin dermatan sulphate were investigated by electron microscopy. Dermatan sulphate filaments oriented orthogonally to collagen fibrils were longer in healing skin than in control skin. In control skin, dermatan sulphate filaments were found among tightly packed collagen fibrils. In contrast, the interfibrillar gaps between each collagen fibril were enlarged in healing skin; elongated dermatan sulphate filaments extended from the surface of collagen fibrils across the enlarged gap. These results suggest that the increase in molecular size of decorin dermatan sulphate is important in organizing collagen fibrils separated by enlarged interfibrillar gaps in healing skin.

This paper proposes the concept of the service gateway, which enables contents to introduce content related services to the user. This system can be realized by linking distributed contents to the related services using content ID defined by Content ID Forum. A prototype system is described.

A case is reported of the vertebral arterial dissection presenting initially with cerebellar infarction, and which subsequently occurred with subarachnoid hemorrhage 14 days later. A 75-year old male was admitted because of vertigo and ataxia. MR T2-weighted imaging showed a hyperintensity areas on the left cerebellar hemisphere and MR angiography showed multiple stenotic lesions in the left vertebral artery. We diagnosed his illness as dissection of the left vertebral artery and antiplatelet therapy and the blood pressure control were carried out. Fourteen days after the onset, the patient complained of sudden onset of headache and subarachnoid hemorrhage was confirmed on CT scan. Proximal clip occlusion of the left vertebral artery and OA-PICA anastomosis was carried out immediately. The patient was discharged with slight truncal ataxia. We evaluated the features of this vertebral arterial dissection presenting with subarachnoid hemorrhage after ischemic stroke with reference to another reported cases.

Fas (APO-1/CD95), a member of the tumor necrosis factor receptor (TNFR)/nerve growth factor receptor (NGFR) superfamily, is a cell-surface molecule that induces apoptosis upon activation. Fas-associated phosphatase-1 (FAP-1) is a 250-kDa protein tyrosine phosphatase (PTP) that is associated with the negative regulatory domain of Fas (C-terminal 15 amino acids). Human tumor cell lines become resistant to Fas-mediated apoptosis when transfected with FAP-1, indicating that FAP-1 functions as a negative regulator in Fas-mediated death signaling. However, the mechanisms by which FAP-1 inhibits apoptosis are still unclear. In order to determine how FAP-1 affects the signaling mediated by Fas, we set out to identify substrates of FAP-1. Toward this end, we prepared synthetic proteins with either the catalytic domain of FAP-1 (C-terminal 399 amino acids) or its inactive form (Cys2408--Ser) fused to glutathione-S-transferase (GST). Using an in vitro dephosphorylation reaction, we found that FAP-1 dephosphorylates IkappaBalpha. Furthermore, a substrate trapping mutant was found to bind tyrosine-phosphorylated IkappaBalpha. Taken together, our data confirm that IkappaBalpha is a substrate of FAP-1.

To investigate the early event of apoptosis, we monitored the morphological changes in the early stage of Fas-induced apoptosis in the human T-cell lymphoma cell line Jurkat, using confocal microscopy. Morphological changes in the nuclei were observed from 30 min after stimulation, and preceded the changes in the cytoskeleton. This kind of change was enhanced in the presence of EGTA but decreased in the presence of dihydrocytochalasin B, without any changes in caspase-3 activation. During the changes in shape of the cells, the actin cytoskeleton collapsed and shrank in the center. Even though nuclei also changed their shapes in apoptotic cells, they were partially TUNEL-negative, suggesting that they were not yet damaged at the DNA level. Our results suggest that, in the process of apoptosis in Jurkat cells, cell nuclei and cytoskeleton are changed first, then membrane blebbing and caspase-3 activation occur, and fragmentation of chromosomal DNA is last.