Association between commensal bacteria and opportunistic pathogens in the dental plaque of elderly individuals

Opportunistic infections in the oral cavity of the elderly may increase the incidence of systemic disease. The objective of this study was to investigate the differences in the oral bacterial flora between dependent elderly (inpatients) and independent elderly (community-dwelling residents). After multiple variables were taken into account, inpatients had significantly lower detection rates than community-dwelling residents for alpha-streptococci (p < 0.001) and Neisseria (p 0.004), and higher detection rates for Pseudomonas aeruginosa (p 0.024), methicillin-resistant Staphylococcus aureus (MRSA) (p 0.011) and Actinomyces spp. (p 0.005). Among inpatients, the requirement for a high degree of care was related negatively to detection of alpha-streptococci, but was related significantly to detection of P. aeruginosa (p 0.018) or MRSA (p 0.004). Tube-fed inpatients had a significantly lower detection rate for alpha-streptococci (p 0.041) and a higher detection rate for P. aeruginosa (p 0.004) than those who did not require tube feeding. Inpatients with a history of antibiotic use had a significantly lower detection rate for alpha-streptococci (p 0.049) and a higher detection rate for MRSA (p 0.007) than those without a history of antibiotic use. The detection rates for P. aeruginosa or MRSA in inpatients without alpha-streptococci were higher than in inpatients with alpha-streptococci after controlling for age and gender (P. aeruginosa, p 0.006; MRSA, p 0.001). Overall, detection of alpha-streptococci had an inverse correlation with the detection of P. aeruginosa and MRSA in the oral cavity and is likely to be an indicator of pathogenic bacterial infection.     

Antitumor effect of KT6124, a novel derivative of protein kinase inhibitor K-252a and its mechanism of action

Summary Novel derivatives of K-252a, (8R*,9S*,11S*)-(–)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i. p.-i. p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca²⁺-and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparantly exhibited DNA scission both dose-and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases.     

A nationwide survey on transient hyperammonemia in newborn infants in Japan: prognosis of life and neurological outcome.

A nationwide survey of transient hyperammonemia in newborns was carried out in Japan. A total of 18 patients, consisting of 12 male and 6 female infants, were reported from 11 facilities. These neonates exhibited hyperammonemia with plasma ammonia levels in the range from 124 to 6256 micrograms/dl. Four newborn infants of the 18 died in the neonatal period, and an additional one died in the early infancy. Among the 13 infants who were alive at the time of this survey, 6 had neurological sequelae, including mental retardation, spastic quadriplegia and epilepsy. The multivariate analysis revealed that the Apgar score at 1 minute, peak plasma ammonia concentration, birth weight and sex were significant factors affecting the prognosis of life.     

Autocrine growth and tumorigenicity of interleukin 2-dependent helper T cells transfected with IL-2 gene

We introduced a mouse IL-2 cDNA expression vector into an IL-2-dependent mouse helper T cell line HT-2. Transfected cells secreted substantial amounts of IL-2, to which they themselves responded by proliferating without further requirement for exogenous IL-2. The proliferation was a direct function of the cell density and was inhibitable by antibodies against IL-2 or IL-2-R, indicating the autocrine nature of the proliferation. Those producing higher amounts of IL-2 were found to be tumorigenic when inoculated into nude mice. The latency period of tumor development correlated inversely with the level of IL-2 secreted. Tumor cells proliferated in vitro in an IL-2 autocrine fashion indistinguishable from that of the inoculated cells. We thus provide evidence that the aberrant activation of the IL-2 autocrine circuit can lead T cells to malignant transformation.     

Assembly, disassembly, and exchange of glial fibrillary acidic protein

The kinetics and dynamics of glial fibrillary acidic protein (GFAP) assembly was explored by a fluorescence energy transfer assay method. Purified GFAP was stoichiometrically labeled at a single cysteine residue with fluorescein-maleimide. Soluble labeled GFAP in a low ionic strength buffer was assembled into 10 nm filaments by rapidly increasing the ionic strength, and the kinetics of GFAP assembly was monitored by the reduction in fluorescence due to self-quenching of fluorescein. The extent of fluorescence quench correlated with both the formation of 10 nm filament morphology and the amount of protein pelleted at 12,000g. The assembly of GFAP is critically dependent upon both protein and magnesium ion concentration, and at the critical concentration for GFAP assembly is approximately 40 micrograms/ml. Disassembly of GFAP filaments was also observed as a relief of fluorescence quenching after dilution of labeled GFAP filaments. When labeled GFAP filaments were mixed with an excess of unlabeled filaments, a rapid increase of fluorescence was observed, which is due to an exchange of subunits between labeled and unlabeled GFAP filaments. These results indicate that GFAP filaments are dynamic structures and that a small pool of kinetically active unassembled GFAP subunits are in a dynamic equilibrium with assembled GFAP filaments. The ability of GFAP to assemble, disassemble, and undergo subunit exchange has important implications for the organization and dynamics of astroglia cell cytoskeleton during development and in response to injury.     

Non-ketotic hyperglycinaemia due to a deficiency of T-protein in the glycine cleavage system in liver and brain

Non-ketotic hyperglycinaemia was diagnosed in a girl at 3 weeks of age because of the typical clinical presentation, the elevated glycine concentration in urine, plasma and especially in cerebrospinal fluid and the normal profile of organic acids in urine. An EEG showed the typical burst suppression pattern. Therapeutic approaches with either pyridoxine (50 mg d-1) alone or in combination with N5-formyltetrahydrofolate (3 X 3 mg d-1) or with strychnine (0.3 mg per kg body weight) did not result in improvement. In postmortem liver and brain of the patient the overall activity of the glycine cleavage system was deficient; examination of the activity of the individual components of the glycine cleavage system in the tissues revealed that the activity of the T-protein was undetectable, whereas that of the other components and of lipoamide dehydrogenase was normal.     

Angiomyolipoma of the kidney; report of two cases with a low fat component

We report two cases of unilateral renal angiomyolipoma. In both cases, our preoperative diagnosis was renal cell carcinoma because no low density area compatible with a fatty tissue was noted in the tumors. Histological examination revealed both tumors to be angiomyolipoma mainly composed of myomatous cells and immature fat cells.