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Biomedical subjects

Takashi Takenouchi

Publications and source records attributed to Takashi Takenouchi.

5 recordsLinked to original sources

In vitro and in vivo antibacterial activities of CS-023 (RO4908463), a novel parenteral carbapenem.

CS-023 (RO4908463, formerly R-115685) is a novel 1beta-methylcarbapenem with 5-substituted pyrrolidin-3-ylthio groups, including an amidine moiety at the C-2 position. Its antibacterial activity was tested against 1,214 clinical isolates of 32 species and was compared with those of imipenem, meropenem, ceftazidime, ceftriaxone, ampicillin, amikacin, and levofloxacin. CS-023 exhibited a broad spectrum of activity against gram-positive and -negative aerobes and anaerobes, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae (PRSP), beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, and Pseudomonas aeruginosa. CS-023 showed the most potent activity among the compounds tested against P. aeruginosa and MRSA, with MICs at which 90% of isolates tested were inhibited of 4 microg/ml and 8 microg/ml, respectively. CS-023 was stable against hydrolysis by the beta-lactamases from Enterobacter cloacae and Proteus vulgaris. CS-023 also showed potent activity against extended-spectrum beta-lactamase-producing Escherichia coli. The in vivo efficacy of CS-023 was evaluated with a murine systemic infection model induced by 13 strains of gram-positive and -negative pathogens and a lung infection model induced by 2 strains of PRSP (serotypes 6 and 19). Against the systemic infections with PRSP, MRSA, and P. aeruginosa and the lung infections, the efficacy of CS-023 was comparable to those of imipenem/cilastatin and vancomycin (tested against lung infections only) and superior to those of meropenem, ceftriaxone, and ceftazidime (tested against P. aeruginosa infections only). These results suggest that CS-023 has potential for the treatment of nosocomial bacterial infections by gram-positive and -negative pathogens, including MRSA and P. aeruginosa.

Animals↗

Robustifying AdaBoost by adding the naive error rate.

AdaBoost can be derived by sequential minimization of the exponential loss function. It implements the learning process by exponentially reweighting examples according to classification results. However, weights are often too sharply tuned, so that AdaBoost suffers from the nonrobustness and overlearning. Wepropose a new boosting method that is a slight modification of AdaBoost. The loss function is defined by a mixture of the exponential loss and naive error loss functions. As a result, the proposed method incorporates the effect of forgetfulness into AdaBoost. The statistical significance of our method is discussed, and simulations are presented for confirmation.

Algorithms↗

Information geometry of U-Boost and Bregman divergence.

We aim at an extension of AdaBoost to U-Boost, in the paradigm to build a stronger classification machine from a set of weak learning machines. A geometric understanding of the Bregman divergence defined by a generic convex function U leads to the U-Boost method in the framework of information geometry extended to the space of the finite measures over a label set. We propose two versions of U-Boost learning algorithms by taking account of whether the domain is restricted to the space of probability functions. In the sequential step, we observe that the two adjacent and the initial classifiers are associated with a right triangle in the scale via the Bregman divergence, called the Pythagorean relation. This leads to a mild convergence property of the U-Boost algorithm as seen in the expectation-maximization algorithm. Statistical discussions for consistency and robustness elucidate the properties of the U-Boost methods based on a stochastic assumption for training data.

Algorithms↗

Relationship of sports experience and ego development of adolescent Japanese athletes.

This study examined the relationship of sports experience with ego development. A questionnaire was used to assess experience of Crisis, Exploration, and Commitment in the issues of Athletic Performance and of Being a Teammate in 782 adolescent Japanese athletes (423 boys, M age = 15.2 yr.; 359 girls, M age = 15.0 yr.). Their Ego Levels were assessed using the Washington University Sentence Completion Test. Correlations indicated that scores on Crisis, Exploration, and Commitment in the issues of Athletic Performance and Being a Teammate were generally associated with Ego Development. Multiple regression analyses indicated that, for boys, the issue of Athletic Performance was closely associated with Ego Development, while for girls, the issue of Being a Teammate was closely associated with Ego Development. Sports experience with crisis, exploration, and commitment may be related to accommodation, which is, in turn, related to ego development. The sex differences on issues related to ego development may be associated with differences in sex-role development for boys and girls.

Adolescent↗

Properties of extended-spectrum beta-lactamases constructed by site-directed mutagenesis.

Plasmids carrying three types of TEM-type extended-spectrum beta-lactamase (ESBL) genes, encoding TEM-3, TEM-5, and TEM-9, respectively, were constructed by site-directed mutagenesis. ESBL producers were prepared by transformation of Escherichia coli JM109 with a plasmid carrying one gene of either the three TEM types, an SHV-type, or a Toho-1 group gene. This strategy with the same vector and host strain can exclude the contribution of other factors to susceptibility, and is useful in Japan, where few TEM-type ESBL producers have been isolated. In vitro antibacterial activities of 23 beta-lactam antibiotics were tested against the ESBL producers by the agar dilution method, and the results were compared. The minimum inhibitory concentrations (MICs) of penicillins tested were more than 32 micro g/ml against both the parental RTEM and ESBL producers, but they were substantially decreased by a combination with beta-lactamase inhibitors. Compared with the MICs against the ESBL-nonproducing host strain, the MICs of the cephalosporins tested for the ESBL producers were increased more than eight times in most cases and in several cases soared to more than 2048 times against a Toho-1 ESBL producer. On the other hand, the MICs of carbapenem, cephamycin, and penem antibiotics were generally comparable to those against the host strain, and were increased by 32 times at most. Kinetic analysis revealed that extended-spectrum cephalosporins were hydrolyzed only slightly to moderately by the TEM-type ESBLs, while carbapenems and a cephamycin were scarcely hydrolyzed, and rather inhibited or inactivated the mutant enzymes.

Anti-Bacterial Agents↗