Activity of quinolones in the Ames Salmonella TA102 mutagenicity test and other bacterial genotoxicity assays

Eight quinolones were examined for their bacterial mutagenicity in the Ames Salmonella TA102 assay and for their effects in other bacterial genotoxicity assays. In the quantitative Ames plate incorporation assay, all eight quinolones induced His+ deletion reversion in Salmonella tester strain TA102, with maximum reversion observed at about two to eight times the MIC. The quinolones also induced the SOS response. At quinolone concentrations close to the MIC, SOS cell filamentation gene sulA was induced in sulA::lacZ fusion strain Escherichia coli PQ37. RecA-mediated cleavage of lambda repressor in lambda::lacZ fusion strain E. coli BR513 was measurable at about 10 times the MIC, though no induction occurred at 20 micrograms of nalidixic or oxolinic acid per ml. Genotoxicity of quinolones also was observed in the Bacillus subtilis DNA repair assay, in which the mutant strain M45 (recA) was more susceptible to quinolones than its parent strain, H17 (rec+). The results from these analyses indicate that quinolones induce SOS functions and are mutagenic in bacteria; these properties correspond to their antimicrobial activities.     

Hypomethylation of classical satellite DNA and chromosome instability in lymphoblastoid cell lines

To determine possible relationships between DNA hypomethylation and chromosome instability, human lymphoblastoid cell lines from different genetic constitutions were studied with regard to 1) uncoiling and rearrangements, which preferentially affect the heterochromatic segments of chromosomes 1 and 16; 2) the methylation status of the tandemly repetitive sequences (classical satellite and alphoid DNAs) from chromosomes 1 and 16, and of the L1Hs interspersed repetitive sequences. The methylation status largely varied from cell line to cell line, but for a given cell line, the degree of methylation was similar for all the repetitive DNAs studied. Two cell lines, one obtained from a Fanconi anemia patient and the other from an ataxia telangiectasia patient were found to be heavily hypomethylated. The heterochromatic segments of their chromosomes 1 and 16 were more frequently elongated and rearranged than those from other cell lines, which were found to be less hypomethylated. Thus, in these lymphoblastoid cell lines, alterations characterized by uncoiling and rearrangements of heterochromatic segments from chromosomes 1 and 16 seem to correlate with the hypomethylation of their repetitive DNAs. Two-color in situ hybridizations demonstrated that these elongations and rearrangements involved only classical satellite-DNA-containing heterochromatin. This specificity may be related to the excess of breakages affecting the chromosomes carrying these structures in a variety of pathological conditions.     

The neuropeptide red pigment concentrating hormone affects rhythmic pattern generation at multiple sites

The level of LamB protein in the outer membrane of Escherichia coli was derepressed in the absence of a known inducer (maltodextrins) under carbohydrate-limiting conditions in chemostats. LamB protein contributed to the ability of the bacteria to remove sugar from glucose-limited chemostats, and well-characterized lamB mutants with reduced stability constants for glucose were less growth competitive under glucose limitation than those with wild-type affinity. In turn, wild-type bacteria were less growth competitive than lamB mutants with enhanced sugar affinity. In contrast to an earlier report, we found that LamB- bacteria were less able to compete in carbohydrate-limited chemostats (with glucose, lactose, arabinose, or glycerol as the carbon and energy sources) when mixed with LamB+ bacteria. The transport Km for [14C]glucose was affected by the presence or affinity of LamB, but only in chemostat-grown bacteria, with their elevated LamB levels. The pattern of expression of LamB and the advantage it confers for growth on low concentrations of carbohydrates are consistent with a wider role in sugar permeation than simply maltosaccharide transport, and hence the well-known maltoporin activity of LamB is but one facet of its role as the general glycoporin of E. coli. A corollary of these findings is that OmpF/OmpC porins, present at high levels in carbon-limited bacteria, do not provide sufficient permeability to sugars or even glycerol to support high growth rates at low concentrations. Hence, the sugar-binding site of LamB protein is an important contributor to the permeability of the outer membrane to carbohydrates in habitats with low extracellular nutrient concentrations.     

Effects of glucose load on brain extracellular lactate concentration in conscious rats using a microdialysis technique

Changes in the brain lactate concentration in cerebral extracellular fluid (ECF) during intravenous infusion of glucose and local administration of glucose were investigated in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were infused intravenously with either 25% sucrose solution or 25% glucose solution at a rate of 16.6 microliters.min-1.100 g-1 for three hours. The blood glucose concentration reached 17.0 +/- 2.6 mM at the end of the glucose infusion, and brain ECF glucose showed a parallel change with the blood glucose concentration and increased to 2.37 +/- 0.30 mM. However, blood and brain ECF glucose concentrations did not change in animals infused with the sucrose solution. On the other hand, the blood lactate concentration in the glucose-infused group also increased from 0.93 +/- 0.18 mM to 2.85 +/- 0.39 mM at the end of the glucose infusion, which was significantly higher than that measured in the sucrose-infused group. The blood lactate level in the glucose-infused group returned to the basal level by the end of the experiment. Brain ECF lactate concentrations increased from 1.21 +/- 0.06 mM to 1.69 +/- 0.11 mM in glucose-infused animals, but did not change in the sucrose-infused animals. The brain ECF lactate concentration showed a positive correlation with the brain ECF glucose concentration in glucose-infused animals. Another group of rats was administered glucose locally for 90 min after substitution of artificial cerebrospinal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study of patient-related characteristics and outcome after moderate injury

The purpose of all injury care is to restore patients' pre-injury functioning and to facilitate the return to normal activities. The aim of this prospective study was to describe and analyse psychiatric factors and other patient-related characteristics which influence long-term results after moderate injuries. One hundred and sixty-nine injured patients were randomized to go through a comprehensive psychosocial research protocol and to participate in the 12 month follow up. The 49 patients lost to follow-up differed significantly from all other patients. They were more often single, blue-collar workers with a lower educational level and had a less favourable psychosocial background, including alcohol abuse. The 120 patients who completed the follow-up were divided in two groups: the non-recovered group (NR, N = 58), patients reporting limitations in performing their work and/or limitations in carrying out housework and/or in social life, and the recovered group (R, N = 62), patients reporting full recovery or only minor limitations in exercise or sports 12 months after the injury. The NR patients were older (P < 0.05), had a slightly higher injury Severity Score (P < 0.01) and showed signs of depression both during the acute post-injury period and at 1 year follow up (P < 0.001). The multivariate analysis showed that measurements of pain and depression during the acute post-injury period were associated with the functional outcome after 12 months. Co-operation between injury and psychiatric units should be developed to identify patients needing psychosocial or psychiatric support during the early phase of rehabilitation.     

Modeling Solvent Drying of Coated Webs Including the Initial Transient

A complete model for the drying of coated webs. as implemented in the spreadsheet DRYWEB for Lotus and for Excel, is described. The model predicts the temperatures and solvent levels throughout the length of the dryer. The initial transient as the coated web approaches the equilibrium temperature in the consiant rate period is calculated. The coating is divided into slices for a finite difference calculation of solvent diffusion to the surface, using a simple free volume model of diffusion. The semi-empirical constants needed can be found from one or two trial runs. The possible use of infra-red heating in addition to convection heating is included in both the constant and falling rates. The calculation of infra-red energy is discussed. The model assumes that the temperature is uniform from the top of the coating to the bottom of the base, and that assumption is justified.     

Heading towards an advanced signalling system for multimedia,multiparty services in broadband ISDN

Introduction of the broadband integrated services digital network (B-ISDN) will enable network users to make use of advanced multimedia, multiparty services. With this aim in view, RACE II project R2044, MAGIC, is investigating long-term signalling requirements, architecture and protocols for B-ISDN. New service concepts are being developed in MAGIC which will provide more flexibility when compared to narrowband ISDN (N-ISDN). The service requirements and other signalling requirements, such as the separation between call and associated connections at the network-node interface, are used to determine the distribution of functions over the network. The signalling protocols which are used to exchange the signalling information are subsequently developed. These signalling protocols are simulated to prove the performance and the feasibility of call handling concepts