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Biomedical subjects

S Arai

Publications and source records attributed to S Arai.

At least 73 records · Page 4Linked to original sources
PubMed2000

Interleukin-18 in combination with IL-2 enhances natural killer cell activity without inducing large amounts of IFN-gamma in vivo.

Interleukin-18 (IL-18) is known to synergistically enhance murine natural killer (NK) cell activity in vitro when combined with either IL-12 or IL-2. However, it has also been demonstrated that simultaneous administration of IL-18 and IL-12 to mice induces extraordinarily large amounts of interferon-gamma (IFN-gamma) in the serum. In this study, we examined the effects of a combination of IL-18 and IL-2 on in vivo NK cell activation in parallel with the induction of toxicity. In contrast to the IL-18 and IL-12 combination, the combined administration of IL-18 and IL-2 to BALB/c mice for 3 days induced neither high levels of IFN-gamma production nor other visible side effects. When compared with treatment with IL-18 or IL-2 alone, the combined treatment resulted in a significant increase in the number of DX-5 (pan-NK cells marker)-positive cells in spleens and a marked enhancement of splenic NK activity, as determined by standard cytotoxicity assays. Enhanced splenic cytotoxicity generated in the mice treated with both IL-18 and IL-2 was also observed against syngeneic Colon 26 adenocarcinoma cells. Consistent with this in vitro observation, combined treatment produced a significantly stronger inhibitory effect on the pulmonary metastases following i.v. injection of Colon 26 tumor cells than treatment with either cytokine alone. These results suggest that IL-18 combined with IL-2 potentiates in vivo NK cell activity and contributes to inhibition of tumor metastasis without inducing significant toxicity.

Animals↗
PubMed2000

Comprehensive study on G protein alpha-subunits in taste bud cells, with special reference to the occurrence of Galphai2 as a major Galpha species.

Previous studies have identified many cDNA species that encode a variety of G protein alpha-subunits occurring in taste buds. These include the cDNA encoding a taste-bud-specific Galpha, gustducin (G(gust)). Here we carried out comprehensive analyses of Galpha species that occur in the taste buds of rat circumvallate papillae and also in their single cells isolated from the taste buds. Reverse transcriptase-polymerase chain reaction showed the presence of 10 kinds of Galpha cDNAs, including a splice variant of Galphas, among which G(gust), Galphas, Galphai2 and Galphai3 cDNAs were shown to be major species. In situ hybridization and immunohistochemistry showed that Galphai2, as well as G(gust), expressed in a subset of taste bud cells, and the frequency of Galphai2-expression appears to be higher than that of G(gust). Southern analyses of the amplified cDNA from single cells showed that each taste bud cell expresses multiple Galpha mRNA species. For example, some Galphai2-positive cells also express one or more other Galpha species, including Galphas, Galphai3 and G(gust), and there is no apparent correlation in expression among the three Galpha species.

Animals↗
PubMed2000

Development of battery charging system for the FE gun system of HVEM.

We have developed a reliable and efficient battery-charging system for the field emission (FE) gun system of high voltage electron microscopes, where the operating condition of the whole FE gun system can be controlled and monitored through a bi-directional optical fiber system, and the control and monitoring circuits located on the high potential of 1 MV are driven by rechargeable Ni-Cd batteries. The power transmission from ground to the high potential is performed through filter condenser circuit. Under the condition that the filter condenser current is limited to 0.2 A(rms) (root-mean-square value), it is possible to transmit the maximum power as high as 65 W, which is enough for the daily operation of the FE gun system. The charging circuit has a function of protecting the batteries from over-charging.

Journal Article↗
PubMed2000

Blockade of Salmonella enteritidis passage across the basolateral barriers of human intestinal epithelial cells by specific antibody.

Antibodies specific to Salmonella enteritidis (S.E.) were obtained from immunized egg yolk, and their protective effects against S.E. were studied by using monolayer-cultured human intestinal epithelial cells, Caco-2 and T84. The Salmonella adherence and entry to the cells were partially inhibited by the antibodies. The antibodies inhibited the decrease in transepithelial electrical resistance (TEER) of the intestinal epithelial monolayers and IL-8 secretion of the cells induced by S.E. invasion. Also, the antibodies blocked the penetration of bacteria through the cell layer although they did not inhibit the growth of bacteria in the cells. Confocal microscopic photographs revealed the bacteria in the infected monolayer cells were bound to antibodies. These results indicate that anti-S.E. antibodies may protect the cells from destruction induced by S.E. invasion in intestinal epithelial cells in addition to the partial inhibition of adhesion and invasion of S.E. at the cell surface. Passive antibodies against invasive bacteria would be useful to prevent the migration of S.E. to blood not only at the cell surface but also inside of intestinal epithelial cells.

Animals↗
PubMed2000

Transfusion-acquired, autochthonous human babesiosis in Japan: isolation of Babesia microti-like parasites with hu-RBC-SCID mice.

We have isolated piroplasms from a patient who developed the first case of human babesiosis in Japan by using NOD/shi-scid mice whose circulating erythrocytes (RBCs) had been replaced with human RBCs (hu-RBC-SCID mice). Following inoculation of the patient's blood specimen into hu-RBC-SCID mice, parasites proliferated within the human RBCs in the mice, resulting in a high level of parasitemia. Parasite DNA was prepared from blood samples of the patient and the mice, and the nuclear small-subunit rRNA gene (rDNA) was amplified and sequenced. Both DNA samples gave rise to identical sequences which showed the highest degree of homology (99.2%) with the Babesia microti rDNA. Because the patient had received a blood transfusion before the onset of babesiosis, we investigated the eight donors who were involved. Their archived blood samples were analyzed for specific antibody and parasite DNA; only a single donor was found to be positive by both tests, and the parasite rDNA sequence from the donor coincided with that derived from the patient. The donor's serum exhibited a high antibody titer against the isolate from the patient, whereas it exhibited only a weak cross-reaction against B. microti strains isolated in the United States. We conclude that the first Japanese babesiosis case occurred due to a blood transfusion and that the etiological agent is an indigenous Japanese parasite which may be a geographical variant of B. microti. Our results also demonstrated the usefulness of hu-RBC-SCID mice for isolation of parasites from humans and for maintenance of the parasite infectivity for human RBCs.

Animals↗
PubMed2000

In-depth mutational analysis of the promyelocytic leukemia zinc finger BTB/POZ domain reveals motifs and residues required for biological and transcriptional functions.

The promyelocytic leukemia zinc finger (PLZF) protein is a transcription factor disrupted in patients with t(11;17)(q23;q21)-associated acute promyelocytic leukemia. PLZF contains an N-terminal BTB/POZ domain which is required for dimerization, transcriptional repression, formation of high-molecular-weight DNA-protein complexes, nuclear sublocalization, and growth suppression. X-ray crystallographic data show that the PLZF BTB/POZ domain forms an obligate homodimer via an extensive interface. In addition, the dimer possesses several highly conserved features, including a charged pocket, a hydrophobic monomer core, an exposed hydrophobic surface on the floor of the dimer, and two negatively charged surface patches. To determine the role of these structures, mutational analysis of the BTB/POZ domain was performed. We found that point mutations in conserved residues that disrupt the dimer interface or the monomer core result in a misfolded nonfunctional protein. Mutation of key residues from the exposed hydrophobic surface suggests that these are also important for the stability of PLZF complexes. The integrity of the charged-pocket region was crucial for proper folding of the BTB/POZ domain. In addition, the pocket was critical for the ability of the BTB/POZ domain to repress transcription. Alteration of charged-pocket residue arginine 49 to a glutamine (mutant R49Q) yields a domain that can still dimerize but activates rather than represses transcription. In the context of full-length PLZF, a properly folded BTB/POZ domain was required for all PLZF functions. However, PLZF with the single pocket mutation R49Q repressed transcription, while the double mutant D35N/R49Q could not, despite its ability to dimerize. These results indicate that PLZF requires the BTB/POZ domain for dimerization and the charged pocket for transcriptional repression.

Amino Acid Motifs↗
PubMed2000

The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein.

The ETO protein was originally identified by its fusion to the AML-1 transcription factor in translocation (8;21) associated with the M2 form of acute myeloid leukemia (AML). The resulting AML-1-ETO fusion is an aberrant transcriptional regulator due to the ability of ETO, which does not bind DNA itself, to recruit the transcriptional corepressors N-CoR, SMRT, and Sin3A and histone deacetylases. The promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding transcriptional factor fused to retinoic acid receptor alpha in acute promyelocytic leukemia associated with the (11;17)(q23;q21) translocation. PLZF also mediates transcriptional repression through the actions of corepressors and histone deacetylases. We found that ETO is one of the corepressors recruited by PLZF. The PLZF and ETO proteins associate in vivo and in vitro, and ETO can potentiate transcriptional repression by PLZF. The N-terminal portion of ETO forms complexes with PLZF, while the C-terminal region, which was shown to bind to N-CoR and SMRT, is required for the ability of ETO to augment transcriptional repression by PLZF. The second repression domain (RD2) of PLZF, not the POZ/BTB domain, is necessary to bind to ETO. Corepression by ETO was completely abrogated by histone deacetylase inhibitors. This identifies ETO as a cofactor for a sequence-specific transcription factor and indicates that, like other corepressors, it functions through the action of histone deactylase.

Acute Disease↗
PubMed2000

Isolation and characterization of a novel polysaccharide as a possible allergen occurring in wheat flour.

A new polysaccharide with a molecular weight of 5.0 x 10(4) was isolated as a possible wheat allergen from a water-soluble fraction of flour by affinity chromatography and gel filtration. The isolated polysaccharide was found to be a possible wheat allergen, as it bound specifically to IgE antibodies in the sera of patients allergic to the water-soluble fraction of flour. Chemically, the sugar moiety of the polysaccharide consisted of D-glucose and D-mannose with beta-1,4-linkages in a molar ratio of 4.4:1. Since this mannoglucan is thought to be stable in our body, it would act as a remaining allergen to cause a long-lasting allergic reaction to wheat flour.

Allergens↗
PubMed2000

Heterogeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels.

Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones), including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring <10 microm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A- and C-zones, and measuring up to 40 microm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.

Adult↗
PubMed2000

Effects of antioxidants on induction of apoptosis in bursal cells of Fabricius during in vitro cultivation.

After physically disrupting cell contacts, apoptosis of bursal cells of Fabricius was induced during in vitro cultivation. The percentage of apoptotic cells increased with incubation time and approximately 70% cells represented apoptosis after 6 hr of incubation. The induction of apoptosis was significantly inhibited by treatment of the cells with ascorbic acid (vitamin C), but not with trolox, a vitamin E analog. An intense DNA ladder pattern was shown at 6 hr post-isolation, which is a biochemical hallmark of apoptosis. Treatment of the cells with ascorbic acid inhibited the DNA fragmentation, but trolox did not. To monitor the intracellular production of reactive oxygen species (ROSs), the intensity of fluorescence emitted from DCFH-DA was measured. The intensity of fluorescence from cells incubated for 0.5-2 hr was approximately 2-fold higher than that from cells at 0 hr. The relative intensity of fluorescence decreased immediately after the addition of ascorbic acid to the cells. The intensity from the cells treated with ascorbic acid was 20-30% of that from the control cells at each incubation time. For trolox, the intensity was 50-70% of that from the control cells at each 1 to 2 hr incubation time. When ROSs-induced lipid peroxidation was assessed using cis-parinaric acid (PnA) as a monitor molecule, lipid peroxidation was found to occur in the control cells after isolation of the bursal cells. Treatment of the cells with trolox reduced lipid peroxidation, but treatment with ascorbic acid enhanced peroxidation.

Animals↗
PubMed2000

Involvement of apoptosis in the endotoxemic lesions of the liver and kidneys of piglets.

The involvement of apoptosis was evaluated in lesions of endotoxemic piglets. A single injection with E. coli O111:B4 lipopolysaccharide (LPS) induced foci of coagulative necrosis in the liver and kidneys. No significant change was observed in these organs at 1.5 hr after LPS injection, but at 6 hr, epithelial cells with chromatin condensation or fragmentation and apoptotic bodies were visible. Foci of coagulative necrosis were formed within 24 hr after LPS inoculation. In and adjacent to the necrotic foci, dead hepatocytes with nuclear condensation or fragmentation were scattered. These dead cells were positively stained by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) methods. Electronmicroscopy revealed apoptotic cells with condensed or fragmented homogeneous nuclear chromatin, and necrotic cells with irregularly destroyed nuclei and cytoplasmic membranes. Apoptotic cell death were also observed in parietal cells of the stomach and lymphocytes in the lymphatic system. DNA ladders with approximately 200-bp multimers were observed in hepatic, renal and thymic samples prepared after 6 and 24 hr of LPS injection by agarose gel electrophoresis. These results suggest that apoptosis is involved in the pathology of swine endotoxemia.

Animals↗
PubMed2000

Inhibitory effects of long-wave ultraviolet radiation of isolated chicken liver nuclei on the Mg2+-dependent transition of chromatin structure.

Since the turbidity of nuclear suspensions is known to be correlated with the nuclear morphology, the effects of long-wave ultraviolet (UVA) radiation on Mg2+-dependent structural transition of chromatin in isolated chicken liver nuclei were monitored by measuring the relative turbidity of nuclear suspensions. UVA radiation of the nuclei inhibited the Mg2+-dependent change in relative turbidity of nuclear suspensions in a UVA dose-dependent manner under aerobic conditions but not under N2 conditions. No inhibitory effect of UVA radiation on the change in relative turbidity was observed in the presence of 50 mM NaN3, which scavenges singlet oxygen (1O2) and hydroxyl radicals (*OH). In contrast, 100 mM dimethyl sulfoxide, which primarily scavenges *OH, did not show the inhibitory effect of UVA radiation. The amounts of DNA-protein crosslinks increased with UVA dose under aerobic conditions but not under N2 conditions. The present study showed that UVA radiation of isolated nuclei inhibited the Mg2+-dependent unfolding of condensed chromatin and that O2 is likely to be involved in this process. Furthermore, the formation of DNA-protein crosslinks may contribute to the inhibition.

Animals↗
PubMed2000

Community services landscape in Canada: survey of developmental disability agencies.

A survey of support services for adults with development disabilities living in community settings in Canada was conducted. Information gathered on services and changes occurring in the community services landscape is discussed. Along with a diminution of government's role in funding and guiding service provision, Canada has witnessed the emergence of private-for-profit services, a relatively recent phenomenon in human services. Differences between the private-for-profit and nonprofit sectors are discussed, including a greater propensity in the nonprofit agencies to engage in advocacy and community education. Overall, evidence indicates that some services are beginning to incorporate individualized approaches to funding and support. Implications for government and for services of emergent patterns of support are noted.

Adult↗
PubMed2000

[Detectability of metastatic brain tumors using gadoteridol-enhanced MRI: usefulness of standard-dose T1-weighted spin-echo image with magnetization transfer and enhanced FLAIR].

PURPOSE: The aim of this study was to compare the detectability and image contrast of metastatic brain tumors depicted by T1-weighted MR imaging (T1WI) with the magnetization transfer (MT) technique after the administration of a standard dose(MT-SD-T1WI) or T1WI without MT after the administration of a double dose of gadoteridol(DD-T1WI). We also assessed the usefulness of enhanced fluid attenuated inversion recovery (FLAIR) for depicting very small metastatic tumors. METHODS: Forty-six MRI procedures were performed in 31 patients with metastatic brain tumors that had been diagnosed clinically and radiologically. An incremental dose technique was used with intravenous injections of 0.1 and 0.1 mmol/kg of gadoteridol. In 28 MRI procedures, enhanced FLAIR was carried out after an MT-SD-T1WI study. RESULTS: Detectability was significantly greater with both MT-SD-T1WI and DD-T1WI than with SD-T1WI. However, there was no significant difference between MT-SD- and DD-T1WI. Although an MT pulse increased the contrast between the enhanced tumor and white matter, the contrast between edema and white matter was decreased. Both MT-SD- and DD-T1WI showed small but conspicuous enhanced foci, but we could not determine whether these were vessels or small metastases on the brain surface. However, enhanced FLAIR only demonstrated foci that were thought to be small metastases. CONCLUSIONS: MT-SD- and DD-T1WI had equal ability to detect metastatic brain tumors. Enhanced FLAIR was useful for assessing very small metastases on the brain surface.

Adult↗
PubMed2000

[A case study of alpha feto protein (AFP)-producing gastric carcinoma with multiple liver metastases, in which chemotherapy was effective enough to once save a life in rapid decline].

A 57 year-old man visited our hospital with general fatigue and a sensation of abdominal fullness. He had lost 10 kg in body weight during the previous 3 months. Between admission and the time the diagnosis of AFP-producing gastric carcinoma with multiple liver metastases was made, his condition deteriorated quickly due to the rapid growth of the liver metastases. Combined chemotherapy consisting of cisplatin and 5-FU was given, and was so effective that the patient recovered well and both serum AFP level and the size of the swollen liver decreased markedly. However, about a month after being discharged, he experienced a relapse and was readmitted. After obtaining informed consent, chemotherapy consisting of methotrexate and 5-FU was started. Though the level of tumor markers and LDH decreased significantly, he died of hepatic failure. We think that this case is worthy of notice because it shows the effectiveness and limitations of chemotherapy in a situation where the condition of a patient is deteriorating quickly due to rapid extension of an AFP-producing gastric carcinoma.

Adenocarcinoma↗
PubMed2000

Efficacy of primary percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients aged > or = 80 years.

The therapeutic result of primary percutaneous transluminal coronary angioplasty (PTCA) in the elderly was assessed in 20 of 44 patients > or = 80 years old (range 81-92 years, mean age 84 +/- 3 years) with acute myocardial infarction who underwent primary PTCA and the results compared with 194 younger patients (< 80 years) who underwent primary PTCA during the same period. In-hospital prognosis, and long-term outcomes were investigated. Emergency coronary angiography was performed in 47.7% of the patients with acute myocardial infarction in the elderly group with 45.5% receiving primary PTCA. Primary PTCA was successful in 95.0% of the elderly group, showing no significant difference from the younger group. In-hospital mortality showed no significant difference between the elderly group and the younger group (5.0% vs 4.1%). However, the incidences of pump failure of the heart and bleeding complication requiring blood transfusion were higher in the elderly group during hospitalization. The 2-year survival rate for the elderly group was 82.5 +/- 9.3%, which was better than previous studies. These results suggest that primary PTCA has a good success rate in the elderly patients with acute myocardial infarction, and decreases the in-hospital mortality and improves the long-term outcome. However, this study was conducted retrospectively in a small group of patients. The efficacy of primary PTCA for the elderly remains to be clarified in a larger prospective trial.

Age Factors↗
PubMed2000

Canadian Independent Living Centres: impact on the community.

There is now widespread interest in developing social policies and practices that are grounded in principles of independent living. The Independent Living (IL) paradigm reflects a shift in thinking away from traditional approaches to supporting persons with disabilities. Independent Living Centres (ILCs), which started in the early 1970s in the United States, and in the 1980s in Canada, are now a major force in the promotion of the IL concept worldwide. The guiding principles of these consumer-driven centres include: promoting an empowerment philosophy that incorporates consumer control/self-direction over decision-making; offering cross-disability support; providing options/choice and flexibility; and encouraging inclusion and full participation. Despite their prevalence, a surprisingly limited body of research exists on the impact of ILCs. A survey was used to investigate the impact of ILCs in Canada on their communities of interest (groups connected to the ILCs). Surveys were sent to formal organizations, informal groups, and family/friends. A final response rate of 52.6% was achieved (111 of 211 surveys returned). Overall, moderate to good levels of familiarity, involvement, and impact were found. The results affirmed the importance of independent living centres to individual empowerment, community change, and the IL movement.

Activities of Daily Living↗