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M Tsuji

Publications and source records attributed to M Tsuji.

At least 55 records · Page 3Linked to original sources

In vitro antibody response to the tetrapeptide repeats of Plasmodium falciparum circumsporozoite protein by splenocytes from mice infected with P. yoelii yoelii.

The antibody response to the recombinant protein, R32tet32, which contained the repetitive sequence (NANP)n of Plasmodium falciparum CSP was determined in C57BL/6 mice during the course of nonlethal infection with Plasmodium yoelii 17X. Marked suppression of the IgG antibody response to R32tet32 occurred when mice were immunized at peak parasitemia (on day 16). In vitro antibody responses of spleen cells from acutely infected mice to R32tet32 were similarly suppressed. Stimulation of normal spleen cells cultured for 5 days with 100 ng/ml of R32tet32 gave an optimal IgG antibody response, but spleen cells from infected mice obtained at peak parasitemia failed to respond to a broad range of antigen concentrations. Cocultivation studies employing enriched lymphocyte populations from infected and uninfected C57BL/6 mice indicated that both T and B cells from infected mice were defective in their response to R32tet32. The response to the repetitive region was restored by the addition of recombinant mouse interleukin-2 (IL-2) at a dose of 50 U/ml to cultures of spleen cells from infected mice.

Animals↗

Progress toward a malaria vaccine: efficient induction of protective anti-malaria immunity.

Malaria can be a very severe disease, particularly in young children, pregnant women (mostly in primipara), and malaria naïve adults, and currently ranks among the most prevalent infections in tropical and subtropical areas throughout the world. The widespread occurrence and the increased incidence of malaria in many countries, caused by drug-resistant parasites (Plasmodium falciparum and P. vivax) and insecticide-resistant vectors (Anopheles mosquitoes), indicate the need to develop new methods of controlling this disease. Experimental vaccination with irradiated sporozoites can protect animals and humans against the disease, demonstrating the feasibility of developing an effective malaria vaccine. However, developing a universally effective, long lasting vaccine against this parasitic disease has been a difficult task, due to several problems. One difficulty stems from the complexity of the parasite's life cycle. During their life cycle, malaria parasites change their residence within the host, thus avoiding being re-exposed to the same immunological environment. These parasites also possess some distinct antigens, present at different life stages of the parasite, the so-called stage-specific antigens. While some of the stage-specific antigens can induce protective immune responses in the host, these responses are usually genetically restricted, this being another reason for delaying the development of a universally effective vaccine. The stage-specific antigens must be used as immunogens and introduced into the host by using a delivery system that should efficiently induce protective responses against the respective stages. Here we review several research approaches aimed at inducing protective anti-malaria immunity, overcoming the difficulties described above.

Animals↗

[Estimation of daily dietary intake of aluminum].

The daily dietary intake of aluminum was estimated through a total diet study from 1996 to 1998. In ten institutes, total diet study samples were prepared and their aluminum concentration was determined. The average daily intake of aluminum was 3.5 mg and the range was 1.8-8.4 mg. The validity of the analytical result was supported by analyses of certified reference materials.

Aluminum↗

[A case of vaginal implantation of transitional cell carcinoma of the bladder].

An 82-year-old female presented with asymptomatic gross hematuria in June 1997. Urethrocystoscopy revealed a multiple papillary tumor of the bladder and posterior urethra. Histology of the punch biopsy specimens of the tumor revealed transitional cell carcinoma (TCC), grade 2 (G2). CT scan showed no distant metastasis and extravesical invasion. The patient was treated by intravesical instillation of adriamycin (ADM), drip infusion of low dose cisplatin (CDDP) and irradiation of the bladder. As the treatment caused a significant tumor shrinkage, transurethral resection of the tumor was performed. Histologically, the tumor revealed no invasion to the muscular layer of the bladder. In April 1998 she noticed genital bleeding, and a multiple papillary tumor was found on the vaginal wall. Histology of punch biopsy specimens of the vaginal tumor showed non-invasive TCC, G2. MRI and specimens of all layer needle biopsy showed no infiltration outside the bladder wall and the vaginal wall. Irradiation of the cavity of the vagina and uterus was made under the diagnosis of superficial vaginal TCC. We assume that vaginal implantation via irrigating fluid or urine has occurred.

Aged↗

Molecular analysis of Salmonella Enteritidis isolates resistance to ampicillin and streptomycin from three outbreaks of food poisoning in Shiga prefecture.

In 1998 and 1999, there were three outbreaks caused by Salmonella Enteritidis in Shiga Prefecture. One outbreak was suspected to be a diffuse outbreak, caused by frozen cream puffs that had been sold in chain stores throughout Shiga Prefecture between the beginning of September and the beginning of October, 1998. The other outbreaks occurred in May and in August, 1999. All isolates of the three outbreaks showed an identical lysis pattern against the typing phage, though this pattern did not conform to the current scheme, so-called RDNC. In addition all isolates were resistant to ampicillin and streptomycin. However, the patterns of pulsed-field gel electrophoresis strongly indicated that the three outbreaks were actually independent.

Ampicillin↗

An estimation of economic effects of tele-home-care: hospital cost-savings of the elderly.

Tele-home-care (or tele-medicine) is being implemented by the application of multimedia such as CATV and ISDN. In this paper, by focusing on the so-called "social hospitalization of the aged," we carry out an estimation of the extent to which tele-home-care based on multimedia can help in saving the cost of hospitalization of the aged in the future. Estimation consists of the following two parts. First, we estimate the trends of the aged population and their hospital expenses using the regression analysis. Second, we assume that new technology such as multimedia and new medical instruments develop according to a logistic curve. Thus, we estimate the rate of diffusion of CATV and ISDN by logistic curves. Then, by multiplying this number by hospital costs per elderly patient as estimated previously, we have been able to calculate the extent to which hospitalization costs can be saved in the entire economy. Our results indicated that in the year 2050, US$257.3 billion, or nearly 7.4% of total hospitalization costs of the aged could be saved by tele-home-care.

Aged↗

Pretreatment with diazepam suppresses the reduction in defensive freezing behavior induced by fluvoxamine in the conditioned fear stress paradigm in mice.

The effects of the selective serotonin (5-hydroxytryptamine (5-HT)) reuptake inhibitor fluvoxamine, given alone or in combination with the benzodiazepine anxiolytic diazepam on the defensive freezing behavior of mice in the conditioned fear stress paradigm were examined. Fluvoxamine (5-20 mg/kg, i.p.) induced a dose-dependent reduction in freezing behavior. In contrast, while low doses of diazepam (0.125 and 0.25 mg/kg, i.p.) reduced the freezing behavior, such effects were not observed with high doses of diazepam (0.5 and 1 mg/kg, i.p.). In the combination study, fluvoxamine (20 mg/kg, i.p. ) did not reduce the freezing behavior in mice that had been pretreated with diazepam (0.125-1 mg/kg, i.p.). None of the doses of fluvoxamine and diazepam used in the present study had any effects on motor activity under non-stressed conditions. These results suggest that benzodiazepines may negatively influence the clinical efficacy of selective 5-HT reuptake inhibitors in the treatment of anxiety disorders.

Animals↗

Roles of pulsatile release of LH in the development and maintenance of corpus luteum function in the goat.

The roles of the pulsatile release of LH in the functional development and maintenance of the corpus luteum (CL) during the estrus cycle in the goat were examined using a potent GnRH antagonist. In Experiment 1, to assess the inhibitory effects of the GnRH antagonist on the release of LH during the estrus cycle, 9 goats were divided into 3 groups. Goats in Group I received only saline on Days 0 (day of ovulation), 5, 10 and 15. Goats in Group II received the GnRH antagonist (50 microg/kg, s.c.) on the days mentioned for Group I to inhibit endogenous LH during the periods of luteal development and maintenance. Goats in Group III received saline on Days 0 and 5 and then the GnRH antagonist on Days 10 and 15 to inhibit LH during the period of luteal maintenance. Serial blood sampling took place on Days 1, 3, 5, 8, 13 and 18 to characterize the LH pulses. The LH pulses were observed throughout the estrus cycle in Group I but were completely abolished in Group II. In Group III, the pulsatile release of LH was observed from Day 1 to 8, but the LH pulses were completely abolished on Days 13 and 18. In Experiment 2, 16 goats were divided into the same 3 groups as in Experiment 1 to examine the effects of the GnRH antagonist on the luteal function. The concentration of progesterone in the plasma in Group I increased after ovulation, reached a maximum level around Day 12, and subsequently returned to the basal level on Day 17. The concentrations of progesterone in Group II rose after ovulation, but reached a plateau around Day 6 and maintained the level up to Day 9, then rapidly decreased from Day 9 to 10 to the basal level. The concentrations of progesterone in Group II were lower on Days 7 to 15 than those in Group I (P<0.01). The concentrations of progesterone in Group III increased after ovulation, reached a maximum level around Day 8, then dropped from Day 10 to 13 to the basal level. The concentrations of progesterone in Group III on Days 11 to 15 were lower than those in Group I (P<0.05 on Day 11, P<0.01 on Days 12 to 15). These results demonstrate that endogenous LH is essential for normal development and maintenance of the CL function during the estrus cycle in the goat. Further, this study suggests that while the functional maintenance of the caprine CL depends entirely on LH support, such functional dependence during early CL development is only partial.

Animals↗

Host-virus interactions during malaria infection in hepatitis B virus transgenic mice.

We have previously shown that hepatitis B virus (HBV) replication is abolished in the liver of HBV transgenic mice by inflammatory cytokines induced by HBV-specific cytotoxic T cells and during unrelated viral infections of the liver. We now report that intrahepatic HBV replication is also inhibited in mice infected by the malaria species Plasmodium yoelii 17X NL. P. yoelii infection triggers an intrahepatic inflammatory response characterized by the influx of natural killer cells, macrophages, and T cells. During this process, interferon (IFN)-gamma and IFN-alpha/beta suppress HBV gene expression and replication in the liver. Collectively, the data suggest that malaria infection might influence the course and pathogenesis of HBV infection in coinfected humans.

Alanine Transaminase↗

Response of murine gamma delta T cells to the synthetic polypeptide poly-Glu50Tyr50.

Random heterocopolymers of glutamic acid and tyrosine (pEY) evoke strong, genetically controlled immune responses in certain mouse strains. We found that pE50Y50 also stimulated polyclonal proliferation of normal gamma delta, but not alpha beta, T cells. Proliferation of gamma delta T cells did not require prior immunization with this Ag nor the presence of alpha beta T cells, but was enhanced by IL-2. The gamma delta T cell response proceeded in the absence of accessory cells, MHC class II, beta 2-microglobulin, or TAP-1, suggesting that Ag presentation by MHC class I/II molecules and peptide processing are not required. Among normal splenocytes, as with gamma delta T cell hybridomas, the response was strongest with V gamma 1+ gamma delta T cells, and in comparison with related polypeptides, pE50Y50 provided the strongest stimulus for these cells. TCR gene transfer into a TCR-deficient alpha beta T cell showed that besides the TCR, no other components unique to gamma delta T cells are needed. Furthermore, interactions between only the T cells and pE50Y50 were sufficient to bring about the response. Thus, pE50Y50 elicited a response distinct from those of T cells to processed/presented peptides or superantigens, consistent with a mechanism of Ig-like ligand recognition of gamma delta T cells. Direct stimulation by ligands resembling pE50Y50 may thus selectively evoke contributions of gamma delta T cells to the host response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

alpha -galactosylceramide-activated Valpha 14 natural killer T cells mediate protection against murine malaria.

Natural killer T (NKT) cells are a unique population of lymphocytes that coexpress a semiinvariant T cell and natural killer cell receptors, which are particularly abundant in the liver. To investigate the possible effect of these cells on the development of the liver stages of malaria parasites, a glycolipid, alpha-galactosylceramide (alpha-GalCer), known to selectively activate Valpha14 NKT cells in the context of CD1d molecules, was administered to sporozoite-inoculated mice. The administration of alpha-GalCer resulted in rapid, strong antimalaria activity, inhibiting the development of the intrahepatocytic stages of the rodent malaria parasites Plasmodium yoelii and Plasmodium berghei. The antimalaria activity mediated by alpha-GalCer is stage-specific, since the course of blood-stage-induced infection was not inhibited by administration of this glycolipid. Furthermore, it was determined that IFN-gamma is essential for the antimalaria activity mediated by the glycolipid. Taken together, our results provide the clear evidence that NKT cells can mediate protection against an intracellular microbial infection.

Animals↗

Immunization and infection change the number of recombination activating gene (RAG)-expressing B cells in the periphery by altering immature lymphocyte production.

Recombination activating gene (RAG) expression in peripheral B cells increases after immunization with (4-hydroxy-3-nitrophenyl) acetyl coupled to chicken gamma globulin (NP-CGG) in alum. This increase could result from reinduction of RAG expression or, alternatively, from accumulation of RAG-expressing immature B cells in the periphery. We have used mice that carry a green fluorescent protein (GFP) RAG indicator transgene (RAG2-GFP) to characterize the RAG-expressing B cells in immunized spleens. Most of the RAG2-GFP-expressing B cells in unimmunized spleen are immature B cells. Injection with NP-CGG in alum initially suppresses lymphopoiesis in the bone marrow and decreases the number of immature RAG2-GFP-expressing B cells in the spleen. Recovery of lymphopoiesis in the bone marrow coincides with accumulation of RAG-expressing immature B cells in the spleen. Most of the RAG-expressing cells that accumulate in the spleen after immunization do not proliferate and they are not germinal center cells. Neither the initial suppression of lymphopoiesis nor the subsequent accumulation of RAG-expressing cells in the spleen is antigen dependent, since similar changes are seen with alum alone. Furthermore, such changes in the numbers of developing and circulating immature lymphoid cells are seen after injection with complete Freund's adjuvant or malaria infection. Our experiments suggest that adjuvants and infectious agents cause previously unappreciated alterations in lymphopoiesis resulting in the accumulation of RAG-expressing immature B cells in the spleen.

Adjuvants, Immunologic↗

Cutting edge: the IgG response to the circumsporozoite protein is MHC class II-dependent and CD1d-independent: exploring the role of GPIs in NK T cell activation and antimalarial responses.

Biochemical analysis has suggested that self GPI anchors are the main natural ligand associated with mouse CD1d molecules. A recent study reported that Valpha14+ NK T cells responded to self as well as foreign (parasite-derived) GPIs in a CD1d-dependent manner. It further reported that the IgG response to the Plasmodium berghei malarial circumsporozoite (CS) protein was severely impaired in CD1d-deficient mice, leading to a model whereby NK T cells, upon recognition of CD1d molecules presenting the CS-derived GPI anchor, provide help for B cells secreting anti-CS Abs. We tested this model by comparing the anti-CS Ab responses of wild-type, CD1d-deficient, and MHC class II-deficient mice. We found that the IgG response to the CS protein was solely MHC class II-dependent. Furthermore, by measuring the response of a broad panel of CD1d-autoreactive T cells to GPI-deficient CD1d-expressing cells, we found that GPIs were not required for autoreactive responses.

Animals↗

The novel kappa-opioid receptor agonist TRK-820 has no affect on the development of antinociceptive tolerance to morphine in mice.

The effects of the novel kappa-opioid receptor agonist 17-cyclopropylmethyl-3,14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl)acrylamido+ ++]morphinan hydrochloride (TRK-820) on the development of antinociceptive tolerance to morphine were investigated in mice and compared with those of trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)-cyclohexyl) benzenacetamide methane sulfonate hydrochloride (U-50,488H), a well-defined exogenous kappa-opioid receptor agonist. Morphine (1. 25-20 mg/kg, s.c.) produced a dose-related antinociceptive effect in the 51 degrees C warm-plate test. Daily treatment with morphine (10 mg/kg, s.c.) resulted in the development of antinociceptive tolerance. The development of antinociceptive tolerance to morphine was dose-dependently suppressed by the co-administration of U-50, 488H (1-10 mg/kg, s.c.) with morphine, but not TRK-820 (0.003-0.03 mg/kg, s.c.). These results suggest that TRK-820-sensitive kappa-opioid receptor subtypes may not be involved in modulating the development of antinociceptive tolerance to morphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Neuroprotective effect of alpha-phenyl-N-tert-butylnitrone in gerbil hippocampus is mediated by the mitogen-activated protein kinase pathway and heat shock proteins.

alpha-Phenyl-N-tert-butylnitrone (PBN), a spin trap, is known as a protective agent against delayed-neuronal death after ischemia-reperfusion. To investigate this neuroprotective effect of PBN, we examined the effect of PBN on the mitogen-activated protein kinase (MAPK) signaling pathway and the expression of heat shock proteins (HSPs) in the gerbil hippocampus following transient (5 min) ischemia. Immunoblot analysis revealed that intraperitoneal (i. p.) injection of PBN (200 mg/kg) enhanced the activation of extracellular-response kinase (ERK) and suppressed the activation of stress-activated protein kinase/c-Jun N-terminal protein kinase (SAPK/JNK) and p38 mitogen-activated protein kinase (p38) at 6 h after ischemia. Elevated levels of HSP27 and HSP70 were seen at the same period. These data suggest that PBN protects against delayed-neuronal death not only by its inherent radical-trapping activity but also by regulating the MAPK pathway and up-regulating HSPs.

Animals↗

Different effects of 5-HT1A receptor agonists and benzodiazepine anxiolytics on the emotional state of naive and stressed mice: a study using the hole-board test.

OBJECTIVES: The effects of 5-HT(1A) receptor agonists on the emotional behavior of naive or stressed mice were examined and compared with those of benzodiazepine anxiolytics. METHODS: Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e. total locomotor activity, numbers and duration of rearing and head-dipping and latency to the first head-dipping, using an automatic holeboard apparatus. RESULTS: The 5-HT(1A) receptor full agonists flesinoxan (0.03-1 mg/kg, IP) and 8-OH-DPAT (0.03-1 mg/kg, IP), and the partial agonist buspirone (0.3-10 mg/kg, IP) dose-dependently decreased all of the exploratory behaviors. Significant decreases in both the number and duration of head-dips, and an increase in the latency to head-dipping were observed at 30 min after exposure to acute restraint stress (60 min). These emotional changes were scarcely improved by post-stress treatment with 5-HT(1A) receptor agonists, at doses that alone did not produce a significant behavioral effect. In contrast, pretreatment with flesinoxan (0.1-1 mg/kg, IP) or 8-OH-DPAT (0.1-1 mg/kg, IP) 24 h prior to exposure to stress dose-dependently suppressed the decrease in various exploratory behaviors that was observed immediately after the exposure to acute restraint stress. Moreover, pretreatment with buspirone (1-10 mg/kg, IP) 24 h prior to exposure to stress also significantly suppressed the decrease in rearing behavior and the increase in head-dip latency. However, changes in the emotional response to stress stimuli were not observed in mice that had been pretreated with the benzodiazepine anxiolytics diazepam (0.1-1 mg/kg, IP) and chlordiazepoxide (2-8 mg/kg, IP). CONCLUSIONS: The present study clearly demonstrates that the behavioral effects of 5-HT(1A) receptor agonists in both naive and stressed mice were quite different from those of benzodiazepine anxiolytics, as previously reported by us. Notably, 5-HT(1A) receptor agonists but not benzodiazepine anxiolytics protect against various emotional changes produced by stress stimuli, and the results suggest that activation of 5-HT(1A) receptors may facilitate some mechanism(s) involved in the recognition of and/or ability to cope with stressful situation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

A novel kappa-opioid receptor agonist, TRK-820, blocks the development of physical dependence on morphine in mice.

The effects of a novel kappa-opioid receptor agonist, TRK-820, on the development of physical dependence on morphine were investigated in mice in comparison with those of U-50,488H. A marked body weight loss and several withdrawal signs were observed following naloxone challenge in morphine-dependent mice. Co-injection of TRK-820 (0.003-0.03 mg/kg, s.c.) but not U-50,488H (1-10 mg/kg, s.c.) during chronic morphine treatment dose-dependently suppressed the naloxone-precipitated body weight loss, jumping, wet dog shakes and diarrhea. These results suggest that TRK-820-sensitive kappa-opioid receptor subtypes may play a significant role in modulating the development of physical dependence on morphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗