Biomedical subjects

Kenichi Aoki

Publications and source records attributed to Kenichi Aoki.

17 recordsLinked to original sources

PubMed2006

A mixed strategy model for the emergence and intensification of social learning in a periodically changing natural environment.

Based on a population genetic model of mixed strategies determined by alleles of small effect, we derive conditions for the evolution of social learning in an infinite-state environment that changes periodically over time. Each mixed strategy is defined by the probabilities that an organism will commit itself to individual learning, social learning, or innate behavior. We identify the convergent stable strategies (CSS) by a numerical adaptive dynamics method and then check the evolutionary stability (ESS) of these strategies. A strategy that is simultaneously a CSS and an ESS is called an attractive ESS (AESS). For certain parameter sets, a bifurcation diagram shows that the pure individual learning strategy is the unique AESS for short periods of environmental change, a mixed learning strategy is the unique AESS for intermediate periods, and a mixed learning strategy (with a relatively large social learning component) and the pure innate strategy are both AESS's for long periods. This result entails that, once social learning emerges during a transient era of intermediate environmental periodicity, a subsequent elongation of the period may result in the intensification of social learning, rather than a return to innate behavior.

Genotype↗

PubMed2006

Cultural coevolution of norm adoption and enforcement when punishers are rewarded or non-punishers are punished.

A number of studies have shown that social norms can be maintained at a high frequency when norm-violators are punished. However, there remains the problem of how norm-adopters and punishers coevolve within a single group. We develop a recursive system to examine the coevolution of norm-adopters and punishers where the viability of punishers is enhanced by one of two "metanorms": (1) Norm-observers reward punishers for punishing norm-violators (Reward Model); (2) Punishers punish non-punishers (Punishment Model). Both models generate a bistable system and each is characterized in phenotype frequency space by a distinct region of attraction to the equilibrium consisting of only norm-adopting punishers. Using a Monte Carlo simulation, we find that cultural drift may allow norm-adopters and punishers to coevolve from invasion into this region of attraction, resulting in their fixation. This coevolution typically occurs across a wider range of conditions under the reward- than the punishment-based metanorm. We also show that, under appropriate conditions, a large negative statistical association between the two traits may evolve only under the Reward Model. Furthermore, for each metanorm, a population of norm-adopters who always observe the norm can be locally stable over a continuum of punishment frequencies.

Cultural Evolution↗

PubMed2005

Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway.

The Janus kinase (Jak)-Stat pathway plays an essential role in cytokine signaling. Granulocyte colony-stimulating factor (G-CSF) promotes granulopoiesis and granulocytic differentiation, and Stat3 is the principle Stat protein activated by G-CSF. Upon treatment with G-CSF, the interleukin-3-dependent cell line 32D clone 3(32Dcl3) differentiates into neutrophils, and 32Dcl3 cells expressing dominant-negative Stat3 (32Dcl3/DNStat3) proliferate in G-CSF without differentiation. Gene expression profile and quantitative PCR analysis of G-CSF-stimulated cell lines revealed that the expression of C/EBPalpha was up-regulated by the activation of Stat3. In addition, activated Stat3 bound to CCAAT/enhancer-binding protein (C/EBP)alpha, leading to the enhancement of the transcription activity of C/EBPalpha. Conditional expression of C/EBPalpha in 32Dcl3/DNStat3 cells after G-CSF stimulation abolishes the G-CSF-dependent cell proliferation and induces granulocytic differentiation. Although granulocyte-specific genes, such as the G-CSF receptor, lysozyme M, and neutrophil gelatinase-associated lipocalin precursor (NGAL) are regulated by Stat3, only NGAL was induced by the restoration of C/EBPalpha after stimulation with G-CSF in 32Dcl3/DNStat3 cells. These results show that one of the major roles of Stat3 in the G-CSF signaling pathway is to augment the function of C/EBPalpha, which is essential for myeloid differentiation. Additionally, cooperation of C/EBPalpha with other Stat3-activated proteins are required for the induction of some G-CSF responsive genes including lysozyme M and the G-CSF receptor.

Acute-Phase Proteins↗

PubMed2004

Evolution of social learning: a mathematical analysis.

Social learning is an important ability seen in a wide range of animals including humans. It has been argued that individual learning, social learning, and innate determination of behavior are favored by natural selection when environmental changes occur at short, intermediate, and long intervals, respectively. Only recently, however, has the hypothesis been examined by means of mathematical models. In this paper, we construct a simple model in which each organism uses one of three genetically determined strategies--it is an individual learner, a social learner or an "innate"--and the three types of organisms are in direct competition with each other. A reduced model, involving only the individual learners and innates, is effectively linear, and we show that by solving the eigenvalue problem of this reduced system we arrive at a good approximation to the global dynamics of the full model. We also study the effect of stochastic environmental changes and reversible mutations among the three strategies. Our results are consistent with the predictions of previous studies. In addition, we identify a critical level of environmental constancy below which only individual and social learners are present.

Animals↗

PubMed2004

Reconstitution of HLA-A*2402-restricted cytomegalovirus-specific T-cells following stem cell transplantation.

Cytomegalovirus (CMV)-specific immune reconstitution early after stem cell transplantation (SCT) was evaluated prospectively by detecting CD8+ T-cells, which recognize the peptide QYDPVAALF in the context of HLA-A*2402. Fifteen allogeneic SCT recipients were included in the study. All recipients and donors were seropositive for CMV and had the HLA-A*2402 allele. CMV-specific T-cells were detected as early as 1 month after transplantation, and their numbers increased to peak levels 2 to 5 months after transplantation. The numbers of CMV-specific T-cells in patients who developed grade II to IV acute graft-versus-host disease (GVHD) and received corticosteroids for acute GVHD were low in the early period after allogeneic SCT. There was a trend toward earlier reconstitution of CMV-specific CD8+ T-cells in allogeneic peripheral blood SCT (PBSCT) patients than in allogeneic bone marrow transplantation patients. The contribution of T-cells in the graft to the recovery of CMV-specific immune responses was also suggested by the finding that the reconstitution of CMV-specific CD8+ T-cells was delayed in CD34-selected autologous PBSCT compared with unpurged autologous PBSCT. The reconstitution of CMV-specific CD8+ T-cells was delayed in patients with CMV disease or recurrent CMV reactivation. These observations suggest that the detection of CMV-specific T-cells with an HLA-peptide tetramer is useful to assess immune reconstitution against CMV and to identify patients at risk for CMV disease or recurrent CMV reactivation after SCT.

Adrenal Cortex Hormones↗

PubMed2003

Dynamics of Epstein-Barr virus load in pyothorax-associated lymphoma.

We treated a 73-year-old man who developed a pyothorax-associated pleural lymphoma after a 52-year history of tuberculous pleuritis. The lymphoma was classified histologically as a diffuse large, B-cell type. Epstein-Barr virus (EBV) was identified in the tumor by immunocytochemical and molecular methods. Chemotherapy both without and with the addition of rituximab was only minimally effective, but adding radiotherapy to chemotherapy reduced the tumor size, resulting in a partial remission. The EBV load measured by a quantitative real-time polymerase chain reaction correlated well with the tumor size and the serum lactate dehydrogenase concentration. Monitoring the EBV load may be useful in the management of pyothorax-associated lymphoma.

Empyema, Pleural↗

PubMed2003

Chronic graft-versus-host disease following varicella-zoster virus infection in allogeneic stem cell transplant recipients.

We describe 2 allogeneic stem cell transplantation patients who developed chronic graft-versus-host disease (GVHD) after dermatomal varicella-zoster virus (VZV) infection. Localized zoster did not respond to oral valaciclovir but did resolve with intravenous aciclovir. However, skin eruptions, eye/oral dryness, and liver dysfunction were observed at the healing stage of localized zoster, suggesting development of GVHD. Intensification of immunosuppressive therapy was required to control GVHD. Quantitative real-time PCR for VZV DNA was used to distinguish liver involvement by chronic GVHD from visceral dissemination of VZV in 1 patient. VZV infection may trigger chronic GVHD after allogeneic stem cell transplantation.

Chickenpox↗

PubMed2003

Neuromuscular blockade can be assessed accelerographically over the vastus medialis muscle in patients positioned prone.

PURPOSE: To study accelerographic monitoring of neuromuscular blockade over the vastus medialis muscle in anesthetized patients in the prone position. METHODS: Sixty adult patients were divided into four groups of 15: prone (P)-post-tetanic count (PTC), P-train-of-four (TOF), supine (S)-PTC or S-TOF group. In the P-PTC and P-TOF groups, the muscular branch of the femoral nerve was stimulated and the movement of the vastus medialis muscle was measured accelerographically. In the S-PTC and S-TOF groups, the depth of neuromuscular blockade was assessed mechanically at the thumb. After administration of vecuronium 0.1 mg.kg(-1), TOF stimuli were delivered every 20 sec in all groups. Onset of neuromuscular blockade (time from vecuronium to the minimum level of T1 (first response of TOF) was compared between the P-PTC or P-TOF group and S-PTC or S-TOF group. Recoveries of PTC and those of TOF were compared between the P-PTC and S-PTC groups and P-TOF and S-TOF groups, respectively. RESULTS: Onset of neuromuscular blockade in the P-PTC or P-TOF group was shorter than in the S-PTC or S-TOF group (132 +/- 43 vs 233 +/- 40 sec, mean +/- SD, P < 0.001). Recoveries of PTC in the P-PTC and S-PTC groups followed a similar time course. Recoveries of T1/control in the P-TOF and S-TOF groups were also comparable. In contrast, train-of-four ratio (T4/T1, TOFR) in the P-TOF group was higher than in the S-TOF group 60-120 min after vecuronium (P < 0.05). CONCLUSIONS: The degree of neuromuscular blockade can be assessed accelerographically over the vastus medialis muscle even when patients are in the prone position. When evaluated accelerographically over the vastus medialis muscle, onset of neuromuscular blockade is quicker and TOFR is higher than that assessed at the thumb.

Analysis of Variance↗

PubMed2003

Limitin, an interferon-like cytokine, transduces inhibitory signals on B-cell growth through activation of Tyk2, but not Stat1, followed by induction and nuclear translocation of Daxx.

OBJECTIVE: Limitin, an interferon-like cytokine, suppresses B lymphopoiesis through ligation of the interferon-alpha/beta (IFN-alpha/beta) receptor. The aim of this study was to examine the intracellular signal transduction pathways activated by limitin. MATERIALS AND METHODS: The effects of limitin on cell growth, the activation of Jak kinase and Stat proteins, and the induction of interferon regulatory factor-1 (IRF-1) and Daxx were examined using the mouse pre-B-cell line 18.81, wild-type, and Tyk2-deficient mouse bone marrow cells. In addition, the change of localization of the Daxx protein after limitin treatment in wild-type and Tyk2-deficient mice was examined. RESULTS: Limitin phosphorylates Tyk2, Jak1, Stat1, and Stat2 and rapidly induces IRF-1 mRNA production. Phosphorylation of Stat1 by limitin is partially dependent on Tyk2. Suppression of B-cell growth by limitin, however, is severely impaired in the absence of Tyk2, whereas it is unaffected by the absence of Stat1. Limitin also induces the expression and nuclear translocation of Daxx, which is essential for IFN-alpha-induced inhibition of B-lymphocyte development. The absence of Tyk2 abrogates this induction of Daxx expression and nuclear translocation. CONCLUSIONS: Limitin suppresses B-cell growth through activation of Tyk2, resulting in the up-regulation and nuclear translocation of Daxx. This limitin-mediated signaling pathway does not require Stat1.

Active Transport, Cell Nucleus↗

PubMed2003

Runaway sexual selection with paternal transmission of the male trait and gene-culture determination of the female preference.

Sexual selection is modeled with a male viability-reducing trait and a female mating preference for that trait both of which are culturally transmitted. Both the male trait and the female preference are transmitted only between same-sex individuals, so that non-random association between the trait and the preference, which would give rise to a Fisherian runaway process, cannot arise. Inclusion of an autosomal gene that confers a female predisposition to acquire a certain preference is shown to allow the coevolution of the male trait and the female preference by a Fisherian process. This holds true even when the female preference has a slight viability cost, provided the male cultural transmission is not perfect. It is also suggested that a Fisherian process can be more easily initiated in these models than in the conventional genetic models. Furthermore, a Fisherian process may cause cultural transmission of female preference to evolve. Additionally, polymorphism can be maintained at the predisposition locus if heterozygous females have a stronger predisposition to acquire the preference than homozygotes. Our models may be applicable to the case when the male trait is a Y-linked genetic or environmentally determined trait.

Animals↗

PubMed2003

The lipocalin 24p3, which is an essential molecule in IL-3 withdrawal-induced apoptosis, is not involved in the G-CSF withdrawal-induced apoptosis.

Many hematopoietic cells undergo apoptosis when deprived of specific cytokines. Lipocalin 24p3, reported to be induced in hematopoietic cells by interleukin 3 (IL-3) depletion, induces hematopoietic cell apoptosis despite the presence of IL-3. As granulocyte colony stimulating factor (G-CSF) depletion also induces the apoptosis of G-CSF-dependent cell line cells, we examined the effect of 24p3 on the apoptotic function induced by G-CSF depletion. 24p3 was induced by the depletion of IL-3, but not G-CSF, in cytokine-dependent cell lines. Although 24p3 suppressed growth induced by IL-3, it did not influence G-CSF-dependent cell growth. These observations show that 24p3 is not involved in the G-CSF withdrawal-induced apoptosis, although it is essential in IL-3 withdrawal-induced apoptosis.

Acute-Phase Proteins↗

PubMed2003

Intracellular signal transduction of interferon on the suppression of haematopoietic progenitor cell growth.

Interferon (IFN)-alpha and IFN-gamma suppress the growth of haematopoietic progenitor cells. IFN-alpha activates Janus kinase-1 (Jak1) and Tyrosine kinase-2 (Tyk2), followed by the phosphorylation of the signal transducers and activators of transcription, Stat1 and Stat2. IFN-gamma activates Jak1 and Jak2, followed by the activation of Stat1. Activated Stats bind the promoter regions of IFN-inducible genes. We evaluated the role of Tyk2 and Stat1 in the IFN-mediated inhibition of haematopoietic progenitor cell growth. While IFN-alpha (1000 U/ml) suppressed the number of granulocyte-macrophage colony-forming units (CFU-GM) or erythroid burst-forming units (BFU-E) from wild-type mouse bone marrow cells, this suppression was partially inhibited by a deficiency in Tyk2 and completely inhibited by a deficiency in Stat1. High levels of IFN-alpha (10,000 U/ml) suppressed the CFU-GM or BFU-E obtained from Stat1-deficient mice, but did not suppress this growth in cells from Tyk2-deficient mice. Stat1 was phosphorylated by IFN-alpha in Tyk2-deficient cells, although the level of phosphorylation was weaker than that observed in wild type mice. Thus, the inhibitory signal on haematopoietic progenitor cells mediated by IFN-alpha may be transduced by two signalling pathways, one regulated by Tyk2 and the other dependent on Stat1. IFN-gamma also suppressed the number of CFU-GM or BFU-E, and this pathway was mediated by IFN-gamma in a Stat1-dependent manner, independently of Tyk2.

Animals↗

PubMed2002

Cutting edge: tyk2 is required for the induction and nuclear translocation of Daxx which regulates IFN-alpha-induced suppression of B lymphocyte formation.

IFN-alpha inhibits B lymphocyte development, and the nuclear protein Daxx has been reported to be essential for this biological activity. We show in this study that IFN-alpha inhibits the clonal proliferation of B lymphocyte progenitors in response to IL-7 in wild-type, but not in tyk2-deficient, mice. In addition, the IFN-alpha-induced up-regulation and nuclear translocation of Daxx are completely abrogated in the absence of tyk2. Therefore, tyk2 is directly involved in IFN-alpha signaling for the induction and translocation of Daxx, which may result in B lymphocyte growth arrest and/or apoptosis.

Active Transport, Cell Nucleus↗

PubMed2002

Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice.

Tyk2 is activated in response to interleukin-12 (IL-12) and is essential for IL-12-induced T-cell function, including interferon-gamma (IFN-gamma) production and Th1 cell differentiation. Because IL-12 is a stimulatory factor for natural killer (NK) cell-mediated cytotoxicity, we examined whether tyk2 is required for IL-12-induced NK cell activity. IL-12-induced NK cell activity in cells from tyk2-deficient mice was drastically reduced compared to that in cells from wild-type mice. IL-18 shares its biologic functions with IL-12. However, the molecular mechanism of IL-18 signaling, which activates an IL-1 receptor-associated kinase and nuclear translocation of nuclear factor-kappaB, is different from that of IL-12. We next examined whether biologic functions induced by IL-18 are affected by the absence of tyk2. NK cell activity and IFN-gamma production induced by IL-18 were reduced by the absence of tyk2. Moreover, the synergistic effect of IL-12 and IL-18 for the production of IFN-gamma was also abrogated by the absence of tyk2. This was partially due to the absence of any up-regulation of the IL-18 receptor treated with IL-12, and it might suggest the presence of the cross-talk between Jak-Stat and mitogen-activated protein kinase pathways in cytokine signaling.

Animals↗

PubMed2002

On Richerson and Boyd's model of cultural evolution by sexual selection.

Richerson and Boyd proposed a model of sexual selection in which both the male trait and the female preference are culturally transmitted. We generalize their model by introducing sex-dependent oblique transmission rates and a fairly comprehensive female preference rule. The model differs markedly from the standard genetic models in that the male trait and the female preference are uncorrelated. Hence, there can be no "sexy son" effect to offset the assumed fertility cost to choosy females. Nevertheless, the cultural processes can support a stable polymorphic equilibrium at which the choosy females are present. Also of interest are the cyclical dynamics observed in the neighborhood of the internal equilibrium.

Cultural Evolution↗

PubMed2002

Therapy-related chronic myelogenous leukaemia following autologous stem cell transplantation for Ewing's sarcoma.

A 17-year-old Japanese woman with Ewing's sarcoma was initially treated with conventional chemotherapy and local irradiation, and then with high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation. Four years later she was diagnosed with chronic myelogenous leukaemia (CML). The BCR/ABL fusion gene was detected in both peripheral blood and bone marrow cells by reverse transcription-polymerase chain reaction, but not in the harvest product of peripheral blood stem cells which were infused at the time of transplantation. This case adds to the accumulating evidence of therapy-related CML developing after high-dose chemotherapy and autologous stem cell transplantation.

Adolescent↗

PubMedDate not supplied

Sexual selection as a cause of human skin colour variation: Darwin's hypothesis revisited.

The dark skin of tropical peoples is likely to be an adaptation to the strong ultraviolet (UV) radiation near the equator, perhaps protecting against sunburn or degradation of folate. By contrast, the adaptive value of light skin is questionable. In particular, the relevance of vitamin D deficiency rickets as a selective factor has been cogently criticized. Population genetic studies on the melanocortin 1 receptor (MC1R) gene (one of the genes responsible for normal human skin colour variation) also cast doubt on the role of positive natural selection in the evolution of light skin. Natural selection may favour dark skin everywhere, though to a lesser extent at higher latitudes. Darwin believed that racial differences in skin colour were caused by sexual selection. Available evidence suggests that in each society a lighter-than-average skin colour is preferred in a sexual partner. Such a preference would generate sexual selection for light skin that counteracts natural selection for dark skin. The observed latitudinal gradient in skin colour may result from the balance between natural and sexual selection.

Cross-Cultural Comparison↗