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Biomedical subjects

K Okabe

Publications and source records attributed to K Okabe.

At least 19 recordsLinked to original sources

The monitoring of insects to maintain biodiversity in Ogawa Fores Reserve.

The results of a biodiversity monitoring program conducted in the Ogawa Forest Reserve and its vicinity, situated in a cool temperate region of Japan, identified three different patterns for species richness. Forests of the region are characterized by a mosaic of secondary deciduous stands of various ages scattered among plantations of conifers. The three different types of change in species richness observed in response to the stand age are as follows: Type I (butterflies, tube-renting bees and wasps, hoverflies, fruit flies, and longicorn beetles), the species diversity was highest in open areas, just after clear-cutting, decreasing with the stand age; Type II (mushrooms and mites associated with them), older stands showed greater diversity than younger stands; and, Type III (moths, oribatid mites, collembolas, carabid beetles, and ants), the number of species did not change greatly with the stand age, though ordination analysis revealed that there was variation in species compositions. These results indicate that combinations of stands of different ages, or heterogeneously arranged stands, can contribute to the maintenance of insect biodiversity at the landscape level.

Animals↗

Parathyroid-hormone-related protein induces expression of receptor activator of NF-{kappa}B ligand in human periodontal ligament cells via a cAMP/protein kinase A-independent pathway.

UNLABELLED: Periodontal ligament (PDL) cells play important roles in root resorption of human deciduous teeth by odontoclasts (osteoclast-like cells). However, it is unclear how PDL cells regulate osteoclastogenesis. We examined the effects of PTHrP, TGF-beta, and EGF, which are all secreted by the tooth germ, on tartrate-resistant acid-phosphatase-positive (TRAP+) cell formation using co-cultures of human PDL cells and mouse spleen cells. Only PTHrP promoted TRAP+ cell formation in co-cultures. PTHrP induced receptor activator of NF-kappaB ligand (RANKL) mRNA expression and slightly reduced osteoprotegerin (OPG) expression in PDL cells. The cAMP/PKA inhibitors Rp-cAMP, H89, and PKI did not affect PTHrP-induced TRAP+ cell formation. The PKC inhibitor, Ro-32-0432, suppressed RANKL expression in PDL cells and PTHrP-induced TRAP+ cell formation. However, this inhibitor directly modulated the number of osteoclast precursors. Thus, PTHrP induces osteoclastogenesis by increasing the relative expression level of RANKL vs. OPG in PDL cells via a cAMP/PKA-independent pathway. ABBREVIATIONS: PTHrP, parathyroid-hormone-related protein; TGF-beta, transforming growth factor-beta; EGF, epidermal growth factor; RANKL, receptor activator of NF-kappaB ligand; OPG, osteoprotegerin; PDL, periodontal ligament; TRAP, tartrate-resistant acid phosphatase; PKA, protein kinase A; PKC, protein kinase C; MAP, mitogen-activated protein; ERK, extracellular signal-regulated kinase; cAMP, cyclic Adenosine 3'5'-Monophosphate.

Acid Phosphatase↗

One-dimensional ordering of ultra-low-density ion beams in a storage ring.

The two-particle model, first introduced by Hasse, is employed to predict the beam temperature at which a one-dimensional ordered state of ions will be established in a cooler storage ring. The proposed state does not have the ions (in the beam frame) at rest, but simply has them not passing each other; i.e., remaining in the same (ordered) sequence. The model is applicable to an ultra-low-density beam where collective Coulomb interactions are negligible. It is pointed out that the nature of the anomalous beam behavior observed in electron-cooling experiments at GSI (Darmstadt) and MSL (Stockholm) is approximately free from such parameters as the lattice design, ion species, beam density, and energy. On the basis of the model, which is put in Hamiltonian form, scaled, and numerically studied, a universal criterion of one-dimensional beam ordering at low line density is derived. Analytic work is employed to explain the numerical results and derives an approximate criterion.

Journal Article↗

Oscillating Coulomb chain in a storage ring.

The dynamic behavior of a bunched one-dimensional crystalline beam is studied theoretically. It is shown that, owing to the existence of momentum dispersion, a Coulomb chain traveling in a storage ring performs a complex periodic oscillation whenever it is exposed to a longitudinal radio-frequency force. The equations of motion are derived to predict the oscillation pattern in an arbitrary lattice structure. The validity of the present theory is confirmed through multiparticle simulations. Various features of an oscillating string beam, such as the lattice-parameter dependence of the orbit, the stability, and critical line density, etc., are also discussed.

Journal Article↗

CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis.

Activated cytotoxic T-cell-mediated hepatocyte apoptosis via Fas/Fas-ligand and perforin/granzyme pathways are believed to involve the model of concanavalin A (ConA)-induced hepatitis. The purpose of the present study is to investigate whether the cytokine response modifier A (crmA) gene effectively inhibits the hepatocyte apoptosis of ConA-induced hepatitis. We examined survival rates, liver pathology, immune histological changes, and cytokine profiles from mice receiving the recombinant adenovirus vectors containing cre and/or crmA genes, transferred to the liver 3 days before ConA injection, and a crmA gene nonexpression control group. Injection of ConA into mice rapidly led to massive hepatocyte apoptosis, and infiltration of leukocytes, especially CD11b(+) inflammatory cells. In contrast, liver damage was dramatically reduced in the mice that expressed the crmA gene. However, infiltration by CD4(+) cells was not affected. The survival of the mice increased significantly to 100% in the treated group versus the control group. Furthermore, we demonstrated that interleukin (IL)-18 plays an important role in ConA-induced hepatitis, and that crmA expression significantly inhibited IL-18 secretion. Our results showed that the crmA gene effectively inhibits apoptosis induced by ConA hepatitis. This indicates a potential therapeutic usage of crmA for protection from cellular damage due to hepatitis.

Adenoviridae↗

Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide.

BACKGROUND: Excessive production of nitric oxide (NO) by the inducible isoform of NO synthase (iNOS) is critically involved in endotoxin (ET)-induced hypotension. Tumor necrosis factor-alpha (TNF-alpha) plays an important role in induction of iNOS. Because activated protein C (APC), a physiological anticoagulant, inhibits TNF-alpha production, it might prevent hypotension by inhibiting excessive production of NO. In this study, we examined this possibility using a rat model of septic shock. METHODS AND RESULTS: Intravenous administration of APC prevented both ET-induced hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-). The hypotension was also inhibited when APC was administered 30 minutes after ET administration. APC inhibited the increases in lung levels of iNOS activity by inhibiting expression of iNOS mRNA in animals given ET. APC significantly inhibited the increases in lung tissue levels of TNF-alpha and expression of TNF-alpha mRNA in animals given ET. Neither DEGR-F.Xa, a selective inhibitor of thrombin generation, nor DIP-APC, an active site-blocked APC, showed any effect on these ET-induced changes. Both inhibition of TNF-alpha production by leukocytopenia and treatment with anti-rat TNF-alpha antibody produced effects similar to those induced by APC. Aminoguanidine, a selective inhibitor of iNOS, inhibited both the hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-) in this animal model. CONCLUSIONS: These observations strongly suggest that APC inhibits iNOS induction by decreasing TNF-alpha production, leading to the prevention of ET-induced hypotension. Furthermore, such effects of APC were not dependent on its anticoagulant effects but rather on its serine protease activity.

Amino Acid Chloromethyl Ketones↗

A serine protease inhibitor, N-alpha-tosyl-l-lysine chloromethyl ketone, prolongs rat hepatic allograft survival.

BACKGROUND: Serine protease inhibitors have profound suppressive effects on cellular and humoral immune responses. We investigated the effect of a serine protease inhibitor, N-alpha-tosyl-l-lysine chloromethyl ketone (TLCK), on hepatic allograft survival in rats. Methods. Orthotopic hepatic transplantation was performed in an ACI (RT1(a))-to-LEW (RT1(1)) rat combination. TLCK was administered continuously at a dose of 4.4 mg/kg/day using an osmotic subcutaneous infusion minipump. RESULTS: TLCK prolonged hepatic allograft survival. Histologic staging of acute rejection based on Banff criteria in TLCK-treated hepatic allografts was significantly lower than in untreated allografts. TLCK significantly reduced serum concentrations of interferon (IFN)-gamma and tumor necrosis factor (TNF) alpha in allograft recipients. TNF-alpha mRNA levels in TLCK-treated allografts were significantly lower than in untreated allografts. TLCK also decreased perforin mRNA levels in hepatic allografts. Hepatic infiltrates eluted from TLCK-treated allografts showed significantly lower cell-mediated lympholytic activity against donor Con A blast cervical lymph node cells than those from untreated allografts. In vitro, TLCK suppressed interleukin-2 production and [(3)H]thymidine incorporation into an allogeneic mixed lymphocyte reaction. CONCLUSION: TLCK suppressed acute allograft rejection, suggesting a novel immunosuppressive strategy for therapy of acute organ rejection.

Animals↗

Differential splenic migration of dendritic cells after immunologic unresponsiveness in rat hepatic allografts induced by pretransplant donor-specific transfusion.

BACKGROUND: Donor dendritic cells migrate into the recipient spleen after hepatic transplantation. We previously reported that immunologic unresponsiveness to rat hepatic allografts can be induced by prior donor-specific blood transfusion (DST). We investigated the phenotype and splenic distribution of donor dendritic cells after allografting and DST. METHODS: Donor dendritic cells were identified with anti-rat dendritic cell (OX-62) and anti-donor class II MHC (RT1B(a)) (OX-76) antibodies. The phenotype of dendritic cells was determined with antibodies to CD45RC, CD62L, and the maturation markers CD80 (B7-1) and CD86 (B7-2). The cytokine profile of sorted CD45RC(+) OX-62(+) and CD45RC(-) OX-62(+) dendritic cells was analyzed by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Pretransplant DST significantly prolonged rat hepatic allograft survival. Immunostaining revealed OX76(+)/OX-62(+) cells in the splenic red pulp of animals receiving pretransplant DST and in the white pulp of untreated animals after transplantation. The ratio of splenic CD45RC(-) OX-62(+) cells to CD45RC(+) OX-62(+) cells was significantly higher in DST recipients than in untreated animals. CD62L, CD80, and CD86 were lower on CD45RC(-) OX-62(+) than CD45RC(+) OX-62(+) cells. RT-PCR revealed that sorted CD45RC(-) OX-62(+) cells expressed interleukin (IL)-4 and IL-10. In contrast, sorted CD45RC(+) OX-62(+) cells expressed only IL-2 and interferon gamma (IFN-gamma). CONCLUSION: Differential splenic migration of CD45RC(-) dendritic cells is associated with immunologic unresponsiveness to rat hepatic allografts.

Animals↗

A method for both mass and individual rearing of fungivorous astigmatid mites (Acari).

Several species of common fungi were assessed as food for fungivorous astigmatid mites. Hypocrea nigricans, Botrytis cinerea and Flammulina velutipes were generally good food sources for most mites examined. Fungal mycelia growing on PDA (potato dextrose agar) medium were not only nutritionally adequate but the system also maintained high humidity through the water-based agar medium. Among acarid mites, most species of Rhizoglyphinae could be reared easily with the method. Although filter-feeding histiostomatid mites do not feed directly on hyphae, some species were successfully maintained with the same method through multiple generations. Presumably, these mites obtained sufficient nutrition from the agar medium and fungal metabolites leaching into it. Most species ultimately produced dispersing heteromorphic deutonymphs on these media. Individual mites were also maintained in isolation within glass rings on fungal colonies. Using this technique, we were able to compare developmental periods, fecundity and survival periods of mites reared under different conditions.

Animal Husbandry↗

Bumblebee commercialization will cause worldwide migration of parasitic mites.

We investigated natural populations of three Japanese native bumblebee species to determine the status of infestation by a tracheal mite, Locustacarus buchneri, which we had earlier detected in introduced commercial colonies of the European bumblebee, Bombus terrestris. We also investigated mite infestation in commercial colonies of a Japanese native species, B. ignitus, which are mass-produced in the Netherlands and reimported into Japan. We detected the mite in both natural and commercial colonies of the Japanese species. Comparison of 555 bp sequences of the mitochondrial DNA (mtDNA) cytochrome oxidase 1 (CO1) gene from the mite showed that there were seven haplotypes, on the basis of combinations of substitutions at eight sites in the gene. The haplotypes of the mites in the Japanese native bumblebees and the haplotypes of the mites in B. terrestris did not overlap; however, mtDNA of mites detected in the commercial colonies of B. ignitus possessed the same sequence as a European haplotype. These results indicate that transportation of bumblebee colonies will cause overseas migration of parasitic mites of different origins.

Animals↗

CD45RC gammadelta T-cell infiltration is associated with immunologic unresponsiveness induced by prior donor-specific blood transfusion in rat hepatic allografts.

Little is known regarding the role of gammadelta(+) T cells in organ transplantation. We previously reported that immunologic unresponsiveness is induced by prior donor-specific blood transfusion (DST) in rat hepatic allografts. We investigated the phenotype and distribution of gammadelta(+) T cells in the hepatic allograft, spleen, and peripheral blood of recipient rats with immunologic unresponsiveness induced by DST. gammadelta(+) T cells were enumerated in allograft livers and spleens by immunostaining and in blood by flow cytometric analysis. The phenotype of gammadelta(+) T cells was determined using CD45RC isoforms derived from alternative mRNA splicing. The cytokine profile of CD45RC(+) and CD45RC(-) gammadelta(+) T cells was analyzed by reverse transcription polymerase chain reaction. The number of gammadelta(+) T cells in hepatic infiltrates in recipient rats pretreated with DST was significantly greater than in untreated animals. This correlated with significantly higher levels of gammadelta T cell receptor (TCR) mRNA in hepatic allografts of DST-treated rats as compared with untreated animals. The gammadelta(+) T cell/alphabeta(+) T-cell ratio increased in hepatic infiltrates in DST-treated recipient rats but not in untreated animals. CD45RC(-)gammadelta(+) T cells were predominantly increased in DST-treated hepatic allografts compared with untreated allografts. Most of the intestinal intraepithelial T cells were CD45RC(-)gammadelta(+). Interleukin (IL)-10 and IL-4 mRNA were detected more in CD45RC(-)gammadelta(+) T cells than CD45RC(+)gammadelta(+) T cells. CD45RC(-)gammadelta(+) T cells infiltrating liver allografts produce Th2-type cytokines and are associated with immunologic unresponsiveness induced by DST.

Acute Disease↗

Determination of glomerular filtration rate per unit renal volume using computerized tomography: correlation with conventional measures of total and divided renal function.

PURPOSE: Previous studies suggest that functional computerized tomography (CT) can measure glomerular filtration rate (GFR) per unit renal volume. We compared this index with conventionally determined GFR measurements. MATERIALS AND METHODS: A total of 16 men and 8 women 63.3 +/- 14.9 years old (range 31 to 88) were studied using with contrast enhanced CT. A single slice of kidney was scanned sequentially after bolus injection (0.5 to 1.0 ml. per second(-1)) of 20 ml. iopamidol (300 mg. iodine per ml.(-1)). GFR per volume of kidney was calculated using a Patlak graphical analysis, and this index was multiplied by renal volume on CT to yield global GFR (ml. per minute(-1)). Divided function was also calculated. GFR and divided renal function were calculated in all cases from radioisotope renography with 99m diethylenetetraminepentaacetic acid. In 12 subjects in whom 24-hour urine collection was possible GFR was also calculated from creatinine clearance. RESULTS: A strong correlation was observed between divided renal function, expressed with respect to the right kidney calculated from CT (52.7 +/- 14.8%, range 19.9% to 97.4%) and by radioisotope renography (51.7 +/- 14.6%, range 18.9% to 92.6%, r = 0.97, p <0.0001). A strong correlation (r = 0.92, p <0.0001) was also seen between global GFR determined by CT (80.1 +/- 43.9 ml. per minute(-1), range 38.2 to 197.9) and creatinine clearance (72.4 +/- 47.5, range 14.6 to 168.5), and was stronger than the correlation between the radioisotope and creatinine clearance method (r = 0.67, p = 0.02) in the same patients. CONCLUSION: Functional CT using nonionic contrast material can measure GFR normalized to renal volume and is an accurate alternative to conventional methods of renal function evaluation.

Adult↗

Pregnancy complicated with Bartter's syndrome: a case report.

Bartter's syndrome is a rare renal disorder, and since there are few case reports of Bartter's syndrome complicating pregnancy are few, the changes of electrolytes and hormonal metabolism during pregnancy are unknown. We describe and discuss the course of pregnancy complicated with Bartter's syndrome.

Adult↗

Structural elucidation of twelve novel esters composed of five fatty acids and three new branched alcohols together with four monoterpenoids from Sancassania shanghaiensis (Acari: Acaridae).

A total of 12 novel esters and four monoterpenoids (rosefuran, (2R,3R)-epoxyneral, and alpha- and beta-acaridials) were detected by GC/MS analyses as the opisthonotal gland components of Sancassania shanghaiensis. The acidic fraction after hydrolysis was composed of five common fatty acids (palmitic, stearic, oleic, linoleic and arachidic acid), while the alcoholic fraction consisted of two major components (C6 and C8 alcohols with branched methyls), together with a trace amount of C9 alcohol. The two major alcohols were identified as new alcohols [(S)-2-methylpentanol and (2S,4S)-2,4-dimethylhexanol] by comparing the physico-chemical data of their 3,5-dinitrobenzoates with those of regio-selectively synthesized alcohols. The C9 alcohol was suggested as (2S,4S)-2,4-dimethylheptanol, based on a structural and biogenetic analogy to the C6 and C8 alcohols. Five of the compounds were each identified by GC to be (S)-2-methylpentyl esters from five fatty acids, and the other five components likewise as (2S,4S)-2,4-dimethylhexyl esters. The remaining two were suggested as (2S,4S)-2,4-dimethylheptyl stearate and linolate.

Alcohols↗

Genistein, a soybean isoflavone, inhibits inward rectifier K(+) channels in rat osteoclasts.

Genistein, a soybean-derived isoflavone with an inhibitory effect on protein tyrosine kinases (PTKs), has been shown to suppress osteoclastic bone resorption. To clarify the mechanisms underlying this action, we investigated the effects of genistein on inward rectifier K(+) current (I(Kir)) in rat osteoclasts by using the whole-cell patch-clamp technique. Extracellularly applied genistein inhibited I(Kir) in a concentration-dependent manner. Physiologically attainable concentrations of genistein inhibited I(Kir). IC(50) values obtained 5 and 10 min after the application of genistein were 54 and 27 microM, respectively. The removal of genistein partially restored the current. Daidzein, an isoflavone without PTK-inhibiting activity, also showed a weak inhibitory effect on I(Kir), but genistin had no effect. Other PTK inhibitors, tyrphostin A25, tyrphostin B42, and tyrphostin B46, inhibited I(Kir), whereas herbimycin A and lavendustin A were without effect. The inactive tyrphostin, A1, showed a similar inhibitory effect as tyrphostin A25. The tyrosine phosphatase inhibitor, orthovanadate, did not affect the inhibitory potency of genistein on I(Kir). The inhibitory action of genistein was unaffected by changing intracellular Ca(2+) concentration ([Ca(2+)]i) or by pretreatment of the cell with GDPbetaS, Rp-cAMPS, okadaic acid, or staurosporine. Therefore the inhibition of I(Kir) by genistein does not depend on PTK inhibition, involvement of changes in [Ca(2+)]i, or secondary interaction with protein kinase A or protein kinase C. Genistein-induced inhibition of I(Kir) would cause membrane depolarization, elevation of [Ca(2+)]i, and inhibition of osteoclastic bone resorption.

Animals↗

In vitro prevention of cell-mediated xeno-graft rejection via the Fas/FasL-pathway in CrmA-transducted porcine kidney cells.

Cell-mediated cytotoxicity may be involved in delayed and/or chronic xenograft rejection in which apoptosis is induced in the grafted cells via the Fas/Fas-ligand (FasL) and perforin/granzyme pathways. One barrier to the potential use of xeonogenic grafts for humans may be Fas/FasL-mediated apoptosis, which would be blocked by the gene expression of cytokine response modifier A (CrmA), a cowpox virus gene product. The purpose of this study is to explore whether crmA is an effective candidate gene for inhibiting apoptosis in an in vitro model of xenograft rejection, using Fas-expressing non-primate cells cultured with a soluble recombinant human FasL (sFasL). A recombinant adenovirus vector expressing CrmA (AxCALNLCrmA) was successfully generated with a Cre-mediated switching system. PK15 cells, derived from a porcine kidney and infected with AxCALNLCrmA and/or AxCANCre at a multiplicity of infection (MOI) ranging from 0.1 to 100, were cultured with human sFasL derived from KFL74.18, a human FasL-overexpressed cell line. The gene-expression level of the PK15 cells was confirmed by CrmA-immune staining. Approximately 70% of the control PK15 cells showed induced apoptosis when cultured with sFasL. In contrast, the apoptosis was dramatically reduced in crmA-gene-transduced PK15 cells. The inhibitory effect of apoptosis increased with an increase in the infection dose of AxCANCre. In addition, the activity of caspases 3 and 8 was significantly inhibited in the crmA-transduced cells. These results indicate that CrmA is an effective gene product for inhibiting Fas/FasL-mediated apoptosis, which suggests the potential therapeutic use of its gene transduction to protect against graft damage due to delayed and/or chronic xenograft rejection.

Animals↗

Posttransplant infusion of donor-specific blood induces immunological unresponsiveness in rat hepatic allografts.

BACKGROUND: We previously reported that pretransplant donor-specific blood transfusion (DST) induces CD45RC-CD4+ T cells, Th2-like effector cells, and prolongs rat hepatic allograft survival. Our study investigated the effects of posttransplant DST on rat hepatic allograft survival. METHODS: Three days after transplantation, LEW (RT1(1)) recipient rats with ACI (RT1a) livers were injected i.v. with freshly heparinized donor-specific blood. The time kinetics of CD45RC-CD4+ and CD45RC+CD4+ T cell subsets in hepatic infiltrates were examined. RESULTS: Posttransplant DST significantly prolonged rat hepatic allograft survival. Interferon (IFN)-gamma, interleukin (IL)-12, and IL-18 mRNA levels in hepatic allografts of untreated recipients were significantly greater than in recipients treated with posttransplant DST. However, hepatic allografts of recipients treated with posttransplant DST showed significantly higher IL-4, IL-10, and transforming growth factor (TGF)-beta mRNA levels than untreated recipients. The ratio of CD45RC-CD4+ T cells to CD45RC+CD4+ T cells was significantly higher in hepatic allografts treated with posttransplant DST than in untreated animals. Immunostaining with anti-rat dendritic cell (OX-62) monoclonal antibody revealed that OX-62+ cells were distributed to the splenic red pulp of animals treated with posttransplant DST and to the splenic white pulp in untreated animals. Most OX62+ cells isolated from the spleen of recipients treated with posttransplant DST expressed donor RT1Ba class II major histocompatibility complex antigens, suggesting that OX-62+ cells were of donor origin. CONCLUSION: Posttransplant DST was associated with persistent infiltration of CD45RC-CD4+ T cells, Th2-like effector cells, in rat hepatic allografts, causing immunologic unresponsiveness and establishment of microchimerism in the spleen.

Animals↗

Inhibition of Fas-mediated fulminant hepatitis in CrmA gene-transfected mice.

Hyperimmune response via Fas/Fas-ligand and perforin/granzyme pathways may be essential in pathogenesis of virus-induced fulminant hepatitis. CrmA inhibits activation of caspases and granzyme B, suggesting it may block these pathways. We investigated whether CrmA expression would inhibit Fas-associated lethal hepatitis in mice. We successfully generated AxCALNLCrmA, a recombinant adenovirus expressing CrmA gene with a Cre-mediated switching cassette. We increased CrmA expression level in the liver transfected with AxCALNLCrmA (10(9) pfu) by increasing administration dose (10(7)-10(9) pfu) of AxCANCre, a recombinant, adenovirus-expressing Cre gene. Injection of anti-Fas antibody into the control mice rapidly led to animal death due to massive liver apoptosis, while the apoptosis was dramatically reduced in the CrmA-expressed mice. The animal survival increased with an increase of CrmA expression. The formation of active caspase-3 was markedly inhibited in the crmA-transfected hepatocytes in vitro. These results suggest that crmA is an effective gene that can inhibit immune-related liver apoptosis.

Adenoviridae↗