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1.Mapping the network of ecological interactions is key to understanding the composition, stability, function and dynamics of microbial communities. In recent years various approaches have been used to reveal microbial interaction networks from metagenomic sequencing data, such as time-series analysis, machine learning and statistical techniques. Despite these efforts it is still not possible to capture details of the ecological interactions behind complex microbial dynamics. 2.We developed the sparse S-map method (SSM), which generates a sparse interaction network from a multivariate ecological time-series without presuming any mathematical formulation for the underlying microbial processes. The advantage of the SSM over alternative methodologies is that it fully utilizes the observed data using a framework of empirical dynamic modelling. This makes the SSM robust to non-equilibrium dynamics and underlying complexity (nonlinearity) in microbial processes. 3.We showed that an increase in dataset size or a decrease in observational error improved the accuracy of SSM whereas, the accuracy of a comparative equation-based method was almost unchanged for both cases and equivalent to the SSM at best. Hence, the SSM outperformed a comparative equation-based method when datasets were large and the magnitude of observational errors were small. The results were robust to the magnitude of process noise and the functional forms of inter-specific interactions that we tested. We applied the method to a microbiome data of six mice and found that there were different microbial interaction regimes between young to middle age (4-40 week-old) and middle to old age (36-72 week-old) mice. 4.The complexity of microbial relationships impedes detailed equation-based modeling. Our method provides a powerful alternative framework to infer ecological interaction networks of microbial communities in various environments and will be improved by further developments in metagenomics sequencing technologies leading to increased dataset size and improved accuracy and precision. This article is protected by copyright. All rights reserved.

Accelerated demand for exploration of minerals and development of mining technologies over the past decade could lead to commercial mining of the deep seafloor in the near future. The campaign for conservation of biological diversity claims that there will be impacts of seabed mining to the deep-sea community and suggests a precautionary approach. In this chapter, we summarize the basic characteristics of communities in hydrothermal vent fields and describe the potential impact of resource mining as well as some previous observations on the effect of natural disturbances. We then introduce a model-based approach to determine the resilience of vent communities, thereby predicting if the communities will be vulnerable or robust to disturbances. Resilience of ecological systems is assessed by measuring the time required to recover to the original state prior to being disturbed. A mathematical model capable of predicting resilience would represent an important contribution to the management of these unique ecosystems. However, compared to most terrestrial and shallow water ecosystems, information regarding hydrothermal vent ecosystems, which are typically found at depths of over 1000 m, is limited. We thus focused on connectivity of vent communities through larval dispersal as a key factor for resilience. We will show how our framework can be used as a practical tool to characterize, understand, or predict resilience. The framework presented here can help assess ecological impacts and develop mitigation strategies associated with deep-sea resource mining. We also discuss what will need to be developed further to better achieve these objectives.

We solve the Euclidean Einstein equations with non-Abelian gauge fields of sufficiently large symmetry in various dimensions. In higher-dimensional spaces, we find the solutions which are similar to so-called scalar wormholes. In four-dimensional space-time, we find singular wormhole solutions with infinite Euclidean action. Wormhole solutions in the three-dimensional Einstein-Yang-Mills theory with a Chern-Simons term are also constructed., 16 pages, 10 figures

The decline of the natural ecosystem on the Ogasawara Islands caused by invasive species has been an important environmental problem and projects for eradicating invasive species are currently underway. Some invasive species have proliferated in the host environment and are affecting the material cycle in the ecosystem. If the invasive species were removed from the environment, the material cycle of the ecosystem may be altered and native species that should be protected may be negatively affected. After the introduction of invasive alien species, namely goats and rats, the vegetation declined on Nakoudojima Island, an island that belongs to the Ogasawara Islands. Therefore, in this study, a mathematical model was developed to simulate and analyze the ecosystem changes that occurred following the eradication of goats and rats. When only rats were eradicated, the island’s vegetation changed to grassland but revegetation was delayed and the biomass of the native animal species did not recover significantly. When only goats were eradicated, the vegetation recovered and the biomass of the native animal species increased; however, the island became forested and many native herbaceous plant species became extinct. When goats and rats were eradicated simultaneously, the vegetation recovered and the biomass of the native animal species increased; however, the ecosystem became very unstable and two extreme results were obtained – the vegetation of the entire island changed to either forest or grassland. The results of this study suggest that instead of simply eradicating invasive species, it is necessary to monitor post-eradication changes in the ecosystem and take adaptive measures as required.

The epidemiology of Panton-Valentine leukocidin (PVL)-positive MRSA in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was examined. Three hundred and forty-two CA-MRSA strains that were susceptible to imipenem and cefazolin were isolated from 1107 samples (intravenous catheter, blood, sputum, urine, skin, wound, and pharynx) from outpatients at Showa University Hospital in Japan between September 2009 and March 2017. The PVL gene was detected in 46 of 342 CA-MRSA strains, accounting for 13.5%. The type of SCCmec was determined by detection of each SCCmec-specific region, class complex, and ccr. SCCmec type IV comprised 33 strains, type V comprised 5 strains, type VII comprised 4 strains, and the unclassified type comprised 4 strains. Among the type IV strains, subtype IVa was dominant, comprising 23 of 33 strains, and the remaining 10 strains were of varying subtypes. The SCCmec type III-specific region, CZ049, was amplified in 2 type V strains, 4 type VII strains, and 4 unclassified strains. In 4 unclassified strains, CZ049 and ccr5 were detected, but neither the SCCmec-specific region nor class complex was detected. The PVL-positive rate was lower than that in Western countries. The SCCmec types of PVL-positive CA-MRSA strains were found to vary, indicating a diverse spreading route.

Mapping the network of ecological interactions is key to understanding the composition, stability, function and dynamics of microbial communities. In recent years various approaches have been used to reveal microbial interaction networks from metagenomic sequencing data, such as time-series analysis, machine learning and statistical techniques. Despite these efforts it is still not possible to capture details of the ecological interactions behind complex microbial dynamics.We developed the sparse S-map method (SSM), which generates a sparse interaction network from a multivariate ecological time-series without presuming any mathematical formulation for the underlying microbial processes. The advantage of the SSM over alternative methodologies is that it fully utilizes the observed data using a framework of empirical dynamic modelling. This makes the SSM robust to non-equilibrium dynamics and underlying complexity (nonlinearity) in microbial processes.We showed that an increase in dataset size or a decrease in observational error improved the accuracy of SSM whereas, the accuracy of a comparative equation-based method was almost unchanged for both cases and equivalent to the SSM at best. Hence, the SSM outperformed a comparative equation-based method when datasets were large and the magnitude of observational errors were small. The results were robust to the magnitude of process noise and the functional forms of inter-specific interactions that we tested. We applied the method to a microbiome data of six mice and found that there were different microbial interaction regimes between young to middle age (4-40 week-old) and middle to old age (36-72 week-old) mice.The complexity of microbial relationships impedes detailed equation-based modeling. Our method provides a powerful alternative framework to infer ecological interaction networks of microbial communities in various environments and will be improved by further developments in metagenomics sequencing technologies leading to increased dataset size and improved accuracy and precision.

(60)Co were detected in common octopus specimens collected in the East China Sea in 1996-2005. The source of (60)Co has remained unclear yet. Stable isotope analyses showed that there was no difference in stable Co concentrations between octopus samples with (60)Co and without (60)Co. This result showed that the stable Co in the digestive gland of octopus potentially did not include a trace amount of (60)Co and the source of (60)Co existed independently. Furthermore, investigations of octopus in other area and other species indicated that the origin of the source of (60)Co occurred locally in the restricted area in the East China Sea and not in the coastal area of Japan. Concentrations of (60)Co have annually decreased with shorter half-life than the physical half-life. This decrease tendency suggests that the sources of (60)Co were identical and were temporary dumped into the East China Sea as a solid waste.

We report seven large B cell lymphoma patients showing the involvement of tumor cells with cyclin D3 (CCND3) expression in bone marrow (BM) at the initial diagnosis. All patients presented with B symptoms, splenomegaly, and anemia/thrombocytopenia lacking hemophagocytosis in the BM. Five of the seven patients had suffered from immunological diseases or cancers. The tumor cells were divided into those with a lymphoplasmacytoid or blastoid appearance. Six cases were confirmed to express CD5 antigen on tumor cells. Three cases presented a chromosomal translocation between CCND3 and the immunoglobulin heavy chain (IGH) loci, t(6;14)(p21;q32). Three and two cases showed unmutated and mutated sequences of the variable region of IGH (VH), respectively, and one case showed deletion of an entire segment of VH. Two cases with t(6;14)(p21;q32) showed an unmutated VH sequence and chromosomal translocation within the switch region of IGH. Further studies are required to determine whether CCND3 expression is associated with a unique subset of diffuse large B cell lymphoma.

We report a follicular lymphoma (FL) case presenting the coexistence of two tumor cell subpopulations in lymph node (LN) and bone marrow (BM), which exhibited an inverse pattern of immunoglobulin light (IgL) chain gene rearrangement and expression: Igkappa-lambda+ in LN and Igkappa+lambda- in BM. These tumor clones shared an identical BCL2-IgH recombination, accompanying t(14;18)(q32;q21) translocation, and an identical variable, diversity and joining segments joining with clone-specific VH somatic hypermutations on the untranslocated IgH allele. Our study provides further evidence that FL clones, originating from common progenitor cells, can be developed independently at different sites and with different IgL expression after immune selection.

I conducted computer simulations of food web evolution and investigated the relationship between the duration of food web evolution and the vulnerability to biological invasion. Model food webs without evolution consisted of animal species with a limited number of prey species and producer species with small intrinsic growth rates. Because these species were not resistant to predation pressure, model food webs without evolution were vulnerable to invasion of powerful omnivores, which had a wide range of feeding preference and a high ecological efficiency. In model food webs without evolution, the number of animal species depending on producer species was small. Therefore, if a producer species invaded and disturbed the base of such food webs, few animal species became extinct. However, model food webs with a long time evolution had a structure that a small number of producer species supported a large number of animal species. When a producer species invaded and disturbed the base of such food webs in this state, many species became extinct by an indirect effect. The mean number of prey species of animal species and the mean intrinsic growth rate of producer species increased rapidly in the early stage of evolution. Therefore, in the early stage of food web evolution, food webs were temporarily resistant to invasion of powerful omnivores. However, this resistibility was not maintained for a long time. The result of this study strongly suggests that food webs change with time, and consequently the vulnerability to invasion changes with time.

Communities on oceanic islands are considered to be vulnerable to biological invasion. However, because the detailed structures of such communities have not yet been revealed, the relationship between their vulnerability and structure is not clear. Because such communities evolved without biological invasion, they are expected to have structures different from those of mainland communities, and this difference is expected to affect their vulnerability to invasion. I conducted computer simulations based on a food web model and investigated the difference in structure between mainland and insular model communities, the former of which evolved with frequent invasion and the latter without invasion. In addition, by conducting computer simulations of invasion of these model communities, I investigated the relationship between community structure and vulnerability to biological invasion. The insular model community evolved to have an unstable structure, in that a small number of plant species supported a large number of animal species, and each species in the community had a small biomass. When a plant species invaded and disturbed the base of the insular model community, many animal species relying on the plants easily became extinct. In addition, when a carnivorous species invaded, animal species with small biomass tended to become extinct. Community collapses caused by biological invasion occurred more frequently in the insular model community than in the mainland model community. These results indicated that those communities that evolved without invasion were vulnerable to invasion. The available data on real insular communities suggest that some have reached the endangered state predicted by this model.

It remains unclear how cardioplegic arrest affects surgical results after coronary artery bypass grafting surgery (CABG). This study compares early outcomes after on-pump beating-heart CABG and conventional CABG.From 2002 to 2005, 114 patients underwent on-pump beating-heart CABG. Multivariate logistic regression revealed five characteristics according to which technique is liable to be used: history of cerebral infarction, urgent or emergent operation, lower ejection fraction, preoperative creatine kinase, and lower number of diseased vessels. The early clinical outcome for these patients was compared against 114 conventional CABG patients, matched using a propensity score constructed with these five significant variables and with two nonsignificant variables: history of diabetes mellitus and hypertension.On-pump beating-heart CABG significantly reduced the duration of operation and cardiopulmonary bypass, total blood loss, and peak creatine kinase (p0.05). The number of patients requiring additional intra-aortic balloon pump support was significantly lower in the on-pump beating-heart CABG group (2 versus 13, p0.01). No patients required percutaneous cardiopulmonary support after on-pump beating-heart CABG, whereas 4 patients needed it after conventional CABG. Complete revascularization was significantly lower (42.1% versus 77.2%, p0.0001), but in-hospital mortality was less in the on-pump beating-heart CABG group (2.6% versus 9.6%, p0.05). No significant difference was found in morbidity including stroke, renal failure, mediastinitis, and prolonged ventilation.On-pump beating-heart CABG can be performed safely, including on high-risk patients. Use of cardiopulmonary bypass and the elimination of cardioplegic arrest may be of most benefit to hemodynamically unstable patients.

Most terrestrial plant communities exhibit relatively high species diversity and many competitive species are ubiquitous. Many theoretical studies have been carried out to investigate the coexistence of a few competitive species and in most cases they suggest competitive exclusion. Theoretical studies have revealed that coexistence of even three or four species can be extremely difficult. It has been suggested that the coexistence of many species has been achieved by the fine differences in suitable microhabitats for each species, attributing to niche-separation. So far there is no explicit demonstration of such a coexistence in mathematical and simulation studies. Here we built a simple lattice Lotka-Volterra model of competition by incorporating the minute differences of suitable microhabitats for many species. By applying the site variations in species-specific settlement rates of a seedling, we achieved the coexistence of more than 10 species. This result indicates that competition between many species is avoided by the spatial variations in species-specific microhabitats. Our results demonstrate that coexistence of many species becomes possible by the minute differences in microhabitats. This mechanism should be applicable to many vegetation types, such as temperate forests and grasslands.

Tropical rainforests are known for their extreme biodiversity, posing a challenging problem in tropical ecology. Many hypotheses have been proposed to explain the diversity of tree species, yet our understanding of this phenomenon remains incomplete. Here, we consider the contribution of animal seed dispersers to the species diversity of trees. We built a multi-layer lattice model of trees whose animal seed dispersers are allowed to move only in restricted areas to disperse the tree seeds. We incorporated the effects of seed dispersers in the traditional theory of allopatric speciation on a geological time scale. We modified the lattice model to explicitly examine the coexistence of new tree species and the resulting high biodiversity. The results indicate that both the coexistence and diversified evolution of tree species can be explained by the introduction of animal seed dispersers., Article, ROYAL SOCIETY OPEN SCIENCE.2(10):150330(2015)

Computer simulations of ecosystems are useful for revealing in detail the ecological processes concerned with major bioevents. Unlike empirical approaches, theoretical models allow us to see virtual evolutionary changes in interspecific interactions in a much shorter time as compared with evolutionary experiments. Some recent ecosystem models succeeded in constructing hypothetical ecosystems with high species diversity by introducing low connectance and gradual evolution. Some of these hypothetical ecosystems had similar properties to real ecosystems. Some models incorporated biologically meaningful rules for constructing interspecific interactions, whereas others did not. Both types of model are complementary to each other: which to choose depends on the purpose of the study. Most of the former type of model focused on incorporating biologically realistic processes. They do not aim to mimic the topological features of real ecosystems. It is quite natural that such models did not reproduce ecosys...

A 39-year-old patient with cervical cancer, stage Ia, was successfully treated by total hysterectomy. Then, after sustained neutropenia for more than 4 years and coincident with its exacerbation, the serum lactate dehydrogenase (LD) level started to elevate and reached a plateau. A test for antineutrophil antibody was negative and LD-3-linked IgAkappa, which may be responsible for high LD activity, was confirmed. The absolute number of blood NK cells was reduced, and a diagnosis of nonimmune chronic idiopathic neutropenia of adult was made. The successive occurrence of these 3 disorders may be based on interrelated immunological abnormalities.

A computer simulation based on a food web model was used to examine whether predator–prey interactions facilitate the evolution of larger body size, and if so, what conditions accelerate the body size increase. If predator species were assumed to feed only on smaller prey species, the evolution of larger body size was driven in the food web model. Intra-clade predation (predator–prey relationship within a same clade) accelerated the body size increase in the simulation. When predators and prey belong to the same clade, they tend to have similar body sizes; even a slight increase in prey body size reduces predation. Moreover, in such a case, the former prey readily becomes a predator of its former predator, because their feeding preferences and characters are similar to each other. Such a reversal of predator–prey relationship forces a stepwise increase in the body size of both species in a positive feed back process. The conditions needed for the positive feed back process may exist just after the K/T mass extinction. Thus, the process suggested in this study might explain the rapid evolution of larger body size in mammals at the beginning of the Paleocene.

In order to clarify the effect of the intensity of stochastic disturbance on temporal diversity patterns, computer simulations for biodiversity change have been performed on the basis of three different models, stochastic model by Raup et al. [Raup, D.M., Gould, S.J., Schopf, T.J.M., Simberloff, D.S., 1973. Stochastic models of phylogeny and the evolution of diversity. J. Geol. 81, 525–542], food web model by Yoshida [Yoshida, K., 2002. Long survival of “living fossils” with low taxonomic diversities in an evolving food web. Paleobiology 28, 464–473; Yoshida, K., 2003. Dynamics of evolutionary patterns of clades in food web system model. Ecol. Res. 18, 625–637], and newly developed food web model with probabilistic disturbances (“disturbance model”). The Yoshida's food web model exhibited a high performance for mimicking the mean of real food webs in several properties and could well reproduce certain kinds of diversity patterns recognized in the fossil record, very large clades, “living fossil” clades, and rapidly diversified clades, which could not be reproduced by the stochastic model. The results of the disturbance models showed that, if a species in the system was suffered from a disturbance which kills the species at the probability of about 50%, temporal diversity patterns generated by food web dynamics were broken. However, the survivorship curve for clade and the ratio of clades with sudden extinction were not affected. In addition, even considerably severe disturbance, which reduces the biomass of species of average biomass to half, did not affect temporal diversity patterns investigated. In the disturbance model, a species which suffered a serious loss of its biomass from a disturbance quickly recovered from the damage, and the effect of disturbance hardly propagated in the system. Consequently, disturbances rarely influence the food web dynamics.

Myelodysplastic syndromes (MDS), especially refractory anemia (RA) are very heterogeneous diseases regarding their morphological, biological and clinical features. One important clinical problem is the difficulty of diagnosis. Soluble transferrin receptors (sTfRs) reflect the erythropoietic activity in the bone marrow (BM). To establish whether determination of serum sTfR could be useful for the differential diagnosis between RA and aplastic anemia (AA), we measured the serum sTfR concentrations, BM cellularity and BM erythroblast percentages in 14 untreated AA and 7 untreated RA patients. The serum sTfR levels of the RA patients (820.1 ± 402.8 ng/ml) were significantly higher than those of the AA patients (491.1 ± 195.2 ng/ml; p = 0.0207). However, the serum sTfR values of RA and AA patients also overlapped. A new index, the ‘sTfR-E index’ [the ratio of serum sTfR level (ng/ml) to BM cellularity (%) × BM erythroblasts (%)] is proposed, which is expected to reflect the number of transferrin receptors (TfR) on the cell membrane per BM erythroblast. The sTfR-E index values of the 7 RA patients (0.395 ± 0.234) were significantly lower than those of the 14 AA patients (2.669 ± 1.633; p = 0.0003). The sTfR-E index values of AA and RA patients overlapped only marginally. In conclusion, the sTfR-E index may be a useful new diagnostic tool to distinguish between AA and RA patients.

The evolutionary patterns of animal species clades in an evolving food web system were examined by computer simulation. In this system, each animal species fed on other species according to feeding preference. The food web system evolved via the appearance and extinction of species. The model succeeded in reproducing evolutionary patterns of diversity similar to those seen in the fossil record. This result indicates that the model reproduced the temporal changes of the rates of colonization and extinction of species in the system, which have been decided a priori in the previous stochastic models. In the food web system, the numbers of both predatory and prey species influenced the temporal diversity patterns in each clade in the system. The number of prey species fluctuated strongly, whereas the number of predatory species gradually increased with time. Therefore, temporal diversity patterns were influenced mainly by the number of predatory species. As a result of the gradual increase of the number of predatory species, it was difficult for each clade to maintain its species diversity for a long time. Slight changes of interspecific interaction can sometimes decide the destiny of a clade. When a clade is faced with extinction, if one predatory species of the clade becomes extinct and one or two prey species of the clade appear, the species diversity in the clade increases again. This result indicates that slight changes of interspecific interaction sometimes decide the destiny of a clade.

I used a computer simulation to investigate the effect of evolution of species characteristics on species diversity in an interaction web system. In the system, species interacted with other species neighboring on a hypothetical niche space. The system changed temporally via evolution of species. Species harming other species survived by killing their enemies. However, while the system was dominated by such species, the system was stable and maintained high species diversity. Species not harming other species survived by developing mutualism, as they could not eliminate their enemies. Because such species could attain larger growth rates than species that harmed others, evolution tended toward species that did not harm others. As a result of this evolution, a small group of species with highly developed mutualism filled the carrying capacity of the system. Consequently, the system became unstable, and the diversity in the system decreased suddenly. Mutualism among species did not increase species diversity in the interaction web system.

Mitoxantrone, etoposide and prednisone (MEP)-based regimens using granulocyte colony-stimulating factor (G-CSF) were designed for relapsed and CHOP-resistant diffuse large B-cell lymphomas in a single institution, and the therapeutic effects and adverse reactions were studied. In a total of 49 patients, the MEP regimen had a 41% (9/22) overall response rate compared with 48% (13/27) for the MEP plus carboplatin (C-MEP) regimen (Chi-squared test, P=0.602). Among 38 CHOP-resistant patients, however, the overall response rate to C-MEP [42% (10/24)] was significantly superior compared with MEP [7% (1/14)] (P=0.023), and the overall survival to C-MEP was superior compared with MEP (P=0.088). Taken together, our results, although non-randomized, suggest that a combination of MEP with carboplatin is better than MEP alone in CHOP-resistant diffuse large B-cell lymphomas.

Living fossils are taxonomic groups surviving for a long time without any remarkable morphological change. Most of them retain low taxonomic diversities. Although some of them have survived in refuges to avoid predators and competitors, not all living fossils live in refuges. The survival of these groups, therefore, should be discussed in the context of biological interaction. I carried out computer simulations of a model food web system, in which each species feeds on others according to its feeding preference. The system evolves via evolution of species. In the simulation, some clades, like “living fossils,” survived for a long time with low species diversities. Such clades consisted of species with low evolutionary rates, which result in high predation pressure and intraclade competition for food. Nevertheless, the clades sustainably utilize prey clades and are consequently provided with sufficient food. In addition, because of the low species diversities of the clades, predators of the clades soon become extinct through lack of food. This study strongly suggests that in an evolving food web system, the low evolutionary rates of living fossils allow the long survival of those groups with low taxonomic diversities.

The time evolution of a class of completely integrable discrete Lotka-Volterra system is shown not unique but have two different ways chosen randomly at every step of generation. This uncertainty is consistent with the existence of constants of motion and disappears in both continuous time and ultra discrete limits.

The production of phenylethanoid derivatives in callus and cell suspension cultures of four oleaceous plants, Abeliophyllum distichum, Forsythia suspensa, F. viridissima, and F. koreana was investigated. Of two types of A. distichum cultured cells, the friable fine cells produced only the 4-hydroxyphenylethanoid-type glucoside, cornoside, whereas the small cell aggregates produced the 3,4-dihydroxyphenylethanoid-type glycosides (i.e. verbascoside) predominantly. In the cultured cells of F. suspensa and F. viridissima, the latter-type glucosides were produced predominantly and from those of F. koreana, lignan glucosides with 3,4-dioxygenated phenyl groups were isolated.

Objectives: The relationship between the two CYP2C19 genotype mutations, CYP2C19m1 in exon 5 and CYP2C19m2 in exon 4, and omeprazole hydroxylation phenotype in healthy Japanese volunteers was studied. A simplified method for phenotyp-ing of CYP2C19 with omeprazole was also investigated.Methods: A total of 50 healthy Japanese volunteers were orally administered 20 mg omeprazole (OPZ) after overnight fasting. The area under the serum concentration-time curve (AUC) ratio of OPZ to 5-hydroxy OPZ (OPZ-OH) between 0 and 6 hr after dosing was calculated. After phenotyping, 28 subjects were analyzed for CYP2C19 genotype with the PCR-RFLP method.Results: The ratio of AUC (0-6hOPZ) to AUC (0-6hOPZ-OH) was significantly correlated with the OPZ/OPZ-OH serum concentration ratios, termed hydroxylation index (HI), at 2 and 3 hr after dosing. Twelve out of 50 subjects showed HI values of more than 6 at 3 hr after drug intake and were judged as poor metabolizers (PMs: 24%). Six out of 28 subjects were homozygous for the wild-type (wt/wt) allele in both exon 5 and exon 4 ; 11, heterozygous for the CYP2C19m1 (wt/m1); 5, heterozygous for the CYP2C19m2 (wt/m2); 5, homozygous for the CYP2C19m1 (m1/m1); 1, heterozygous for both defects (m1/m2). The homozygous genotype was compatible with the phenotype of the extensive metabolizer (EMs: wt/wt) and PMs (m1/m1). The heterozygous genotype, however, was not clearly compatible with the phenotype: one out of 11 with wt/m1 genotype was judged as PM. Five subjects with wt/m2 were EMs. The phenotype of one subject with m1/m2 could not be identified due to extremely low serum concentrations of OPZ and OPZ-OH.Discussion: From our findings, genotype and phenotype correlated well among the subjects. Further studies are needed to clarify the relationship between the CYP2C19 genotype and phenotype in subjects with a heterozygous genotype. Care should be taken in phenotyping CYP2C19 with OPZ using a few sampling points since gastric emptying time affects the systemic absorption of OPZ, and hence serum concentrations of the drug especially in the clinical situation are affected by co-administered medicines.

The data for the purification of actual groundwater polluted with tetrachloroethylene by a photocatalytic treatment plant are reported.The pilot plant was very effective in removing tetrachloroethylene (PCE) from water ; the highest PCE removal efficiency was ca. 99%.The results obtained by the experiment were summarized as follows :1) The PCE removal ratio was dependent on the initial PCE concentration in air.2) Removal ratio of PCE in the photocatalytic reactor reached a maximum at the air flow rate of about 7 l/min.3) No organic chlorinated product of the degradation reaction was detected.4) It was confirmed that the photocatalytic activity did not change during the experimental period of 8 months.

Management of the small aortic root is a significant problem for the surgeon with regard to operative technique and selection of the prosthesis. We report on four adults with a small aortic root who underwent aortic valve replacement with a 16-mm CarboMedics bileaflet valve. All patients now lead normal lives. Postoperative Doppler measurements demonstrated an acceptable transprosthetic gradient.

Cardiopulmonary support (CPS) requires durability of the oxygenator. The life span of the oxygenator is affected by various clinical factors, including patient condition, perfusion condition, and equipment usage. Predictors for the durability of oxygenators were evaluated clinically in this study. Thirty-two patients, who had undergone CPS during the last 3 years in our institute were assigned to this study. Fifty oxygenators had been used (Capiox SX in 19, CB Maxima in 23, and AL-6000 in 8). Significant predictors for the durability of oxygenators were evaluated by nonparametric survival analysis and proportional hazards regression analysis. Univariate regression analysis revealed 6 significant predictors for the life span of oxygenators. These were the oxygenator type, type of centrifugal pump, acidosis with blood pH less than 7.35, base excess less than -5, blood glutamic-oxaloacetic transaminase (GOT) levels greater than 1,000 IU, and blood lactate dehydrogenase (LDH) levels greater than 3,000 IU. After multivariate analysis, there remained only 2 significant predictors. An oxygenator used with a noncoated CPS system (Capiox SX with Capiox EBS) proved to have a significantly shorter life span than one used with a heparin-coated system (CB Maxima or AL-6000 with CB BP-80) (hazards ratio, 3.588, p = 0.0065). Patient conditions, which revealed acidosis with less than -5 of base excess, significantly shortened the life of the oxygenator (hazards ratio, 3.595, p = 0.0188).

症例は,19歳男性,1992年9月急性リンパ性白血病(FAB分類ALL L2)と診断しJapan Adult Leukemia study Group (JAL-SG)プロトコールにて治療し完全寛解に到った後,1994年8月,再発しprednisolone, vincristineによる寛解導入療法を行った.その後,cytarabine,l-asparaginaseにて治療し長期間,骨髄抑制が起こり,発熱と潰瘍底を形成し中心部が壊死に陥った皮疹が全身に認められるようになった.皮膚生検を行い,培養の結果Fusarium solaniを検出した.そのため,granulocyte colony-stimulating factor (G-CSF) 350μgを連日静注し,amphotericin B (AMPH)を点滴静注し1mgから開始し40mgまで増量した.しかし,原疾患の悪化に伴いPseudomonas aeruginosaによる敗血症を併発し死亡した.剖検では全身各種臓器にもFusariumによる播種性病変が認められた.とくに肺,消化管,腎,心,膵,筋肉に多発性病変を,また腎は一部梗塞を伴う病変を認めた.今後,免疫不全患者の増加によりこのような弱毒真菌感染症が増加するものと思われた.

Multi-locus sequencing typing (MLST) of Acinetobacter baumannii, isolated at Showa University Hospital, was performed between November 2010 and March 2011. A. baumannii was isolated from 15 patients. Among the 15 isolates, the STs of three isolates were able to be determined, ST76, ST92, and ST146, and belonged to Clonal Complex (CC) 92, the global epidemic clone among carbapenem resistant A. baumannii. The other 12 strains were not applicable to the MLST classification. The ST76 strain was resistant to carbapenems, aminoglycosides, and fluoroquinolones. The ST92 strain was resistant to aminoglycosides and fluoroquinolones. The ST146 strain was resistant to fluoroquinolones. The other 12 strains were susceptible to either of the drugs. Neither the metallo beta lactamase gene (IMP type or VIM2) nor the OXA23 gene was detected in carbapenem resistant A. baumannii. These results indicate that A. baumannii of CC92 has spread as the drug resistant strain in Japan. Monitoring A. baumannii using molecular epidemiology is necessary.

Background. Nafamostat mesilate (FUT-175) is a synthetic serine protease inhibitor that inactivates coagulation, fibrinolysis, and platelet aggregation. Nafamostat mesilate may suppress the blood-foreign surface reaction similar to biocompatible materials by blocking factor XIIa. Methods. We performed an in vitro study of cardiopulmonary bypass (CPB) with fresh human blood among the following three groups: standard CPB sets (C), biocompatible CPB sets (B), and standard CPB sets with FUT-175 (10 mg/L) (F). A clinical study using these same CPB groups also was performed in 45 patients undergoing aortocoronary bypass operations (15 patients each). We injected FUT-175 at 40 mg/h during CPB. Results. In the in vitro study, both groups B and F showed significantly lower levels of coagulation factors, thrombin-antithrombin III complex, fibrinopeptide A, β -thromboglobulin, complement C3a, granulocyte elastase, and free hemoglobin than group C at the conclusion of the study. Thrombin-antithrombin III complex and free hemoglobin in group F also were lower than in group B. The platelet count remained at a higher level in group F than in the other groups. Separation of bradykinin was suppressed most significantly in group F. In the clinical study, group F also showed significantly lower levels of α 2-plasmin inhibitor plasmin complex and C3a than both groups C and B. There were minimal levels of free hemoglobin in group F. Conclusions. Nafamostat mesilate may contribute major beneficial effects toward conservation of blood during CPB and prevention of coagulopathy after CPB.

An obligately barophilic bacterium isolated from intestinal content of a deep-sea fish (Coryphaenoides yaquinae), which was retrieved from a depth of 6100 m in the Northwest Pacific Ocean, swelled in the early-exponential phase, elongated in the midexponential phase, thinned in the late-exponential phase, and shortened in the stationary phase when incubated both at 82.7 MPa and at 41.4 MPa around the optimum growth pressure. The same changes were observed at any pressures where the strain could grow. We propose to call such morphological changes the SETS (swell-elongate-thin-shorten) phenomenon. These results suggest the possibility that the SETS phenomenon might occur in the growth of the strain at high-pressure deep-sea environments.

We isolated two plasmids, pS51A and pS51B which were 5782 bp and 4854 bp in size, respectively, from the third generation cephalosporin-resistant E. cloacae suspected to express metallo-beta-lactamase, and analyzed their structures. These two plasmids encode RNA I/RNA II genes for replication origin, relaxase genes of mobABCD for plasmid transfer, and several open reading frames. According to the classification of mobilizable plasmids by gene organization of the relaxases, pS51A and pS51B belong to the ColE1 superfamily of mobilizable plasmids, commonly detected in Enterobacteriaceae. The metallo-beta-lactamase gene was not identified in either pS51A or pS51B by homology search of the putative open reading frames. Open reading frames encoded in pS51A include E. coli protein L-like, E. coli heat shock protein-like, and E. coli plasmid replication initiation protein-like, and those encoded in pS51B include helix-turn-helix protein-like, E. coli plasmid replication initiation protein-like, and Salmonella replication initiation protein-like. These plasmids are stably maintained in one strain of E. cloacae, thus, the encoded gene functions may confer growth advantage to the host cell.

The effects of calcium antagonists (nifedipine, nicardipine, diltiazem, and verapamil) and prostaglandin E1 (PGE1) on the tension of isolated canine coronary arterial strips were studies. In a solution containing 20 mEq/L of K+, 127 mEq/L of Na+, the tension was increased by 500–1,000 mg with 4 mEq/L of Ca2+. This increase in tension was suppressed by Ca-antagonists and PGE1 dose-dependently. Nifedipine 10−5M, nicardipine 3 X 10−7M, diltiazem 3 X 10−6M, and verapamil 3 X 10−6M completely suppressed the increased tension. The maximal suppression of the tension produced by PGE1 was about 40% at 10−10M. In 20 mEq/L K+ solution (0 mEq/L Ca2+, 37°C), the reduction of the Na+ concentrations from 127 mEq/L to 12 mEq/L increased the tension by 50 to 100 mg. This increase in tension was not suppressed by Ca-antagonists or PGEI. In conclusion, this study demonstrated that Ca-antagonists and PGE1 suppressed an increase in the tension caused by Ca2+ but did not suppress an increase in the tension caused by Na+ reduction.

Trichloroetylene in water was degraded photocatalytically by using thin-film TiO2. The photocatalyst of the thin-film TiO2 was prepared on the surface of quartz tubes by means of sol-gel process. The degradation reaction was studied by using the thin-film TiO2 prepared under the different condition of the calcination temperatures. The blacklight fluorescent lamp and the low pressure mercury lamp were used for the illumination. Under the illumination of the blacklight fluorescent lamp, the TiO2 of anatase accelerated the decomposition reaction rates about two times as fast as the TiO2 of rutile. Under the illumination of the low pressure mercury lamp, the decomposition reaction of trichloroetylene proceeded without the photocatalyst and the addition of the TiO2 of anatase accelerated the reaction a little further. No product of the degradation reaction was detected except CO2 and HCl. The life of the thin-film TiO2 photocatalyst was tested for six months intermittently and it was confirmed that the photocatalytic activity did not change during the experimental period.

The distribution of ofloxacin (OFLX) in the palatal tonsil and maxillary sinus mucosa was quantitatively analyzed. OFLX (100mg), lomefloxacin (100mg), and tosufloxacin (75mg) were administered orally 2 hours before surgery. The tissue concentration of OFLX was 1.61±0.46μg/ml on average and was higher than the serum concentration (0.72±0.21μg/ml), the tissue/serum ratio (2.24) was significant. The tissue concentration of OFLX was higher than that of lomefloxacin and tosufloxacin. In addition, clinical and bacteriological trials on patients with otorhinolaryngological infections was carried out. OFLX was administered orally at a dose 600mg for more than three days. The incidence of stains resistant to OFLX (MIC>3.13μg/ml) was 5.8%. The overall clinical efficacy rate was 86.7% and there were no safety problems. It was concluded that OFLX is a useful drug for treating otorhinolaryngological infections.