Streptococcal infection in the pathogenesis of Beh?et's disease and clinical effects of minocycline on the disease symptoms

Although the precise pathoetiology of Beh?et's disease (BD) remains obscure, patients with BD have a high incidence of chronic infectious foci, indicating an enhanced susceptibility to chronic tonsillitis, and dental caries. Sometimes, clinical symptoms appear after treatment of these foci in BD patients. It is believed that BD might be related to an allergic reaction to a bacterial infection in view of the many clinical symptoms, especially the presence of aphthous and genital ulcerations. An attempt to obtain cutaneous responses to bacterial antigens has been carried out using various vaccines developed from bacteria isolated from the ulcerative lesions and oral cavities of BD patients. BD patients often show intense hypersensitivity to various strains of streptococci, not only by their cutaneous reactions but also by in vitro testing. In this report, we describe our previous studies on the correlation between streptococcal antigens and the pathogenesis of BD and also discuss the recent reports of other authors. The intense hypersensitivity to streptococcal antigens acquired after streptococcal infection is thought to play an important role in the appearance of symptoms in BD patients since the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) was enhanced when stimulated with streptococcal antigen in a culture system. Minocycline, an antibiotic to which certain strains of streptococci are sensitive, reduced the frequency of clinical symptoms in BD patients as well as the production of pro-inflammatory cytokines by BD-PBMC stimulated with streptococcal antigen.     

p53 alteration, proliferating cell nuclear antigen, and nucleolar organizer regions in thymic epithelial tumors

We examined p53 protein expression, p53 gene mutation, proliferating cell nuclear antigen (PCNA), and argyrophilic nuclear organizer regions (AgNOR), in 30 patients with surgically-treated thymic tumors (26 thymoma and 4 thymic carcinoma cases). p53 expression ratio with DO-1 was divided as p53 negative (0% positivity), low expressor (<10% positivity), high expressor (>10% positivity). The incidence of p53 low and high expressor in thymoma were 19% (5/26) and 8% (2/26), respectively. p53 immunopositivity in thymoma was significantly correlated with PCNA labeling index (LI). p53 expression ratio in invasive thymoma (33%) tended to be higher than that in non-invasive thymoma (18%). p53 expression was detected in one of the thymic carcinoma. There were no p53 gene mutations in 15 invasive thymoma, although one of four (25%) thymic carcinomas showed two point mutations. p53 gene alterations seem to be associated with malignant activity of tumor cells, and therefore detection of p53 gene mutations is useful as a diagnostic factor.     

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.     

Isolation and characterization of a novel 5-oxoprolinase (without ATP-hydrolyzing) from Alcaligenes faecalis N-38A

A screening test was undertaken to isolate a microorganism that produced 5-oxoprolinase (without ATP-hydrolyzing). The 5-oxoprolinase (without ATP-hydrolyzing) activity (decyclization activity toward L-pyroglutamate) was found in a cell-free extract of Alcaligenes faecalis N-38A, newly isolated from a soil sample. The enzyme was purified as a homogeneous preparation. The molecular weight of the enzyme was estimated to be 47,000. The decyclization activity was specific for L-pyroglutamate, and independent of ATP and metal ions. The reaction was a reversible one, i.e., cyclization reaction of L-glutamate to yield pyroglutamate was identified.     

Modeling of the pharyngeal muscle in Caenorhabditis elegans based on FitzHugh-Nagumo equations

The pharyngeal pumping motion to send food to the bowel is a rhythmic movement in Caenorhabditis elegans. This paper proposes a simulation-based approach to investigate the mechanisms of rhythm phenomena in the pharyngeal pumping motion. To conduct the simulations, first, we developed a pharyngeal muscle model including 29 cell models which simulate the activity of each cell as a membrane potential based on FitzHugh-Nagumo equations. Then, to compare the response of the model with that of C. elegans, we calculated the electropharyngeogram (EPG), which represents the electrophysiological responses of the pharyngeal cells, using the simulated membrane potentials. The results confirmed that our model could generate the EPG similar to that measured from C. elegans. We proposed a computer simulation of the pumping motion to investigate the mechanisms of rhythm phenomena in living organisms.     

Synthesis and characterization of new bimetallic transition metal oxynitrides: MI-MII-O-N (MI,MII=V,Mo, W and Nb)

A new class of materials, M_I-M_II-O-N (where M_I, M_II = V, Mo, W, and Nb), has been synthesized by nitriding bimetallic oxide precursors with ammonia gas via a temperature programmed reaction. The oxide precursors are prepared by conventional solid state reaction between two appropriate monometallic oxides. The synthesis of the oxynitrides involves passing NH₃ gas over the oxide precursors at a flow rate of 6.80×10² mols^–1 (1000 cm³ min^–1), and raising the temperature at a rate of 8.3×10^–2 Ks^–1 (5K min^–1) to a final temperature which is held constant for a short period of time. The oxynitrides thus obtained are pyrophoric and need to be passivated before exposing them to air. All these new bimetallic oxynitrides have a face centered cubic (f.c.c.) metal arrangement and high values of surface area. Their surface activity is assessed from their ability to chemisorb CO.     

Self-generation of reward by logarithmic transformation of multiple sensor evaluations

Artificial Life and Robotics - Although the design of the reward function in reinforcement learning is important, it is difficult to design a system that can adapt to a variety of environments and...     

Probabilistic nearest neighbor query processing on distributed uncertain data

A nearest neighbor (NN) query, which returns the most similar object to a user-specified query object, plays an important role in a wide range of applications and hence has received considerable attention. In many such applications, e.g., sensor data collection and location-based services, objects are inherently uncertain. Furthermore, due to the ever increasing generation of massive datasets, the importance of distributed databases, which deal with such data objects, has been growing. One emerging challenge is to efficiently process probabilistic NN queries over distributed uncertain databases. The straightforward approach, that each local site forwards its own database to the central server, is communication-expensive, so we have to minimize communication cost for the NN object retrieval. In this paper, we focus on two important queries, namely top-k probable NN queries and probabilistic star queries, and propose efficient algorithms to process them over distributed uncertain databases. Extensive experiments on both real and synthetic data have demonstrated that our algorithms significantly reduce communication cost.