Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017.

TwoGram-negative bacteria were found to produce the newantibacterial antibiotics TAN-1 057 A, B, C arid D. The producing bacteria were characterized and designated as Flexibacter sp. PK-74 and PK-176.Theseantibiotics wereactive against Gram-negativeand Gram-positivebacteria, including methicillin-resistant Staphylococcus aureus. TAN-1 057 A inhibited protein biosynthesis in Escherichia coli and S. aureus.It showed excellent protective effects against an experimental methicillin-resistant S. aureus infection in mice.

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Twonewnucleotide antibiotics, fosfadecin and fosfocytocin, have been isolated from the culture filtrates of Pseudomonas viridiflava PK-5and Pseudomonasfluorescens PK-52, respectively. These antibiotics werepurified by columnchromatographies using adsorption, gel filtration and ion exchange resins. Onthe basis of the spectroscopic and degradation studies, the chemical structures of fosfadecin and fosfocytocin were determined. These antibiotics were either enzymatically or chemically hydrolyzed to generate fosfomycin and a new antibiotic, fosfoxacin, which are also produced in the culture filtrates. They showed antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity of these nucleotide antibiotics was weaker than that of fosfomycin and fosfoxacin.In the course of screening for new antibiotics which inhibit bacterial cell wall biosynthesis, we found that new nucleotide antibiotics, fosfadecin (1) and fosfocytocin (2) were produced by Gram-negative bacteria. These two antibiotics were converted to their nucleoside 5'-monophosphates (5 and 6, respectively), in addition, fosfadecin yielded fosfomycin1) (3) and fosfocytocin yielded a new antibiotic, fosfoxacin (4) (Fig.1).The present paper describes the producing organisms, fermentation, isolation, structure determination and biological activity of these nucleotide antibiotics. Producing OrganismThe fosfadecin-producing strain PK-5 was isolated from a bamboo leaf collected in Yumesaki-cho, Shikama-gun, Hyogo Prefecture, Japan. The fosfocytocin-producing strain PK-52 was isolated from a soil sample collected in Shimotsu-cho, Kaiso-gun, Wakayama Prefecture, Japan.The taxonomical characteristics of strains PK-5 and PK-52 are summarized in Table 1.. Strains PK-5 and PK-52 are Gram-negative rods, motile by polar flagella, metabolize glucose oxidatively, and are catalase-positive.The mol % G+Cof the DNAis 65.1 and 63.7, respectively. Strains PK-5 and PK-52 are considered to belong to the genus Pseudomonas.Strain PK-5 does not accumulate poly-/Miydroxybutyrate as a carbon reserve material, and it produces fluorescent pigment. This strain is also negative for arginine dihydrolase and oxidase. These properties indicate that it should be classified as Pseudomonassyringae or Pseudomonasviridiflava. As strain PK-5 has a polar flagellum, it was identified as P. viridiflava and designated P. viridiflava PK-5.Strain PK-52 does not accumulate poly-/?-hydroxybutyrate and produces fluorescent pigment. It has more than one flagella. It is arginine dihydrolase positive and hydrolyzes gelatin. Fromthese characteristics, 1 Fosfadecin was presented as TAN-930 in Jpn.

In the search for new beta-lactam antibiotics of natural origin, the discoveries of cephamycins and sulfazecins (monobactams) were important turning points in that they accelerated many screening efforts aimed at other new compounds. In our target-directed screening for beta-lactam antibiotics using beta-lactam hypersensitive mutants, we have examined Gram-negative bacteria isolated from natural habitats and have recently reported several types of beta-lactam antibiotics such as cephabacins and formadicins. Here we report a novel antibiotic, lactivicin, found using this system. Although lactivicin has various biological activities commonly observed in beta-lactam antibiotics, it does not possess a beta-lactam ring in its molecule, but has the unique structure of a dicyclic dipeptide.