Search

We demonstrate the fabrication of ultra-low-loss, all-fiber Fabry–Perot cavities that contain a nanofiber section, optimized for cavity quantum electrodynamics. By continuously monitoring the finesse and fiber radius during the fabrication of a nanofiber between two fiber Bragg gratings, we were able to precisely evaluate taper transmission as a function of radius. The resulting cavities have an internal round-trip loss of only 0.31% at a nanofiber waist radius of 207 nm, with a total finesse of 1380, and a maximum expected internal cooperativity of ∼1050 for a cesium atom on the nanofiber surface. Our ability to fabricate such high-finesse nanofiber cavities may open the door for the realization of high-fidelity scalable quantum networks.

We investigated the incidence of anomalies in the vertebral arteries and Circle of Willis with three-dimensional CT angiography in 55 consecutive patients who had undergone an instrumented posterior fusion of the cervical spine.We recorded any peri-operative and post-operative complications. The frequency of congenital anomalies was 30.9%, abnormal vertebral artery blood flow was 58.2% and vertebral artery dominance 40%. The posterior communicating artery was occluded on one side in 41.8% of patients and bilaterally in 38.2%. Variations in the vertebral arteries and Circle of Willis were not significantly related to the presence or absence of posterior communicating arteries. Importantly, 18.2% of patients showed characteristic variations in the Circle of Willis with unilateral vertebral artery stenosis or a dominant vertebral artery, indicating that injury may cause lethal complications. One patient had post-operative cerebellar symptoms due to intra-operative injury of the vertebral artery, and one underwent a different surgical procedure because of insufficient collateral circulation. Pre-operative assessment of the vertebral arteries and Circle of Willis is essential if a posterior spinal fusion with instrumentation is to be carried out safely.Cite this article: Bone Joint J2014;96-B:535–40.

We investigate the microscopic third-order nonlinear optical properties, i.e., the second hyperpolarizabilities (γ), of two different sizes of molecular aggregates with a dendritic, i.e., Bethe-lattice, structure. One possesses a nonfractal structure, while the other has a fractal structure. The aggregate is treated in a two-exciton model composed of two-state monomers coupled to each other by the dipole–dipole interaction. The off-resonant γ of the aggregates are calculated by the numerical Liouville approach, including relaxation effects. The total γ value is partitioned into the contribution of virtual exciton generation, and its spatial contribution to γ is analyzed in relation to the virtual excitation processes in the perturbation theory. It is found that the intermolecular-interaction effect enhances both one- and two-exciton-generation contributions, while the relaxation effect reduces those, although the one- and two-exciton-generation contributions have mutually opposite signs. From the comparison of spatial contributions to γ between the nonfractal and fractal aggregates, an enhancement of the contribution to γ from the periphery to the core is observed in the fractal structure, while such a feature is not observed in the nonfractal structure. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001

We investigate the intermolecular-interaction and damping (among exciton states) effects on the polarizabilities (α) for molecular aggregates with different sizes of planar dendritic, i.e., Bethe-lattice (or Cayley-tree), structures by elucidating the spatial contribution of one-exciton generation to α. The molecular aggregate is treated in the one-exciton model, including the dipole−dipole interaction. The off-resonant α of the molecular aggregate is calculated by the numerical Liouville approach, including the damping effects. The signs of the contribution of intermolecular-interaction (positive) and damping (negative) effects to α are found to be opposite with each other. The magnitude of these effects on α indicates a nonlinear enhancement as the number of monomers increases. These effects on α for the fractal-structured dendritic aggregates are also found to provide distinct spatial contributions for different generations of the dendritic structure in contrast to the case of a non-fractal-structured dendritic aggregate.

1. We investigated the membrane response of the local directionally selective (LDS) interneuron, a nonspiking cell identified in the terminal abdominal ganglion of crayfish, to intracellularly injected current in different regions within the cell by single-electrode, discrete current-clamp experiments. The site of electrode impalement into the cell was visualized in situ together with the cell structure under a dissecting microscope. 2. The LDS interneuron has dendritic branches on both hemiganglia connected by a thick segment crossing the midline. Irrespective of the site of electrode impalement, the interneuron showed outward rectification upon depolarization from the resting potential level. When hyperpolarizing current was injected, a linear relationship was observed between the voltage response of the interneuron and the amount of injected current. Upon large hyperpolarization, however, the interneuron showed inward rectification. 3. The input resistance of the interneuron measured within the linear range of the membrane response was significantly lower in the transverse segment than in lateral dendrites (0.001 < P < 0.01). The time constant of the transient voltage response to step current injection was also significantly shorter in the transverse segment than in the lateral dendrites (0.001 < P < 0.01). 4. Although the regional difference in the input resistance could be accounted for, at least partly, by different geometric conditions of each dendritic branch into which current was injected, the regional difference in the time constant of the membrane response cannot be accounted for by structural differences because the time constant is independent of the membrane area. It is thus suggested that the passive properties of the interneuron membrane that are related to its response time constant show regional variability within the cell.

Uropod motor neurons in the terminal abdominal ganglion of crayfish are continuously excited during the abdominal posture movement so that subthreshold excitatory postsynaptic potentials from the descending statocyst pathway can elicit spike activity in the motor neurons only while the abdominal posture system is in operation. Local nonspiking interneurons in the terminal ganglion were also found to show sustained membrane potential change during the fictive abdominal posture movement. Artificial membrane potential change of these interneurons by intracellular current injection in the same direction as that actually observed during the abdominal movement caused similar excitation of uropod motor neurons. Artificial cancellation of the membrane potential change of these interneurons during the abdominal movement also caused cancellation of the excitation of uropod motor neurons. We concluded that the continuous excitation of uropod motor neurons during the fictive abdominal movement was mediated, at least partly, by the local nonspiking interneurons. Fourteen (36%) out of 39 examined nonspiking interneurons were judged to be involved in the excitation of uropod motor neurons during the fictive abdominal movement. Another 25 interneurons (64%) were found not to be involved in the excitation of motor neurons, although most of them had a strong effect on the uropod motor neuron activity when their membrane potential was changed artificially. The interneurons that were involved in the excitation of motor neurons during the abdominal movement included both of the two major structural types of nonspiking interneurons in the terminal ganglion, i.e., those in the anterolateral portion and those in the posterolateral portion. No strict correlation was found between the structure of nonspiking interneurons and their function in the control of uropod motor neuron activity.

The occurrence of the uropod steering response as one of the equilibrium reflexes to body rolling in crayfish is significantly facilitated if the stimulus is given while the animal is performing the abdominal posture movement. This facilitation of the descending statocyst pathway by the abdominal posture system takes place between the uropod motor neurons and the statocyst interneurons, which directly project from the brain to the terminal abdominal ganglion where the motor neurons originate. To elucidate the synaptic mechanisms underlying the postural facilitation of the steering response, we analyzed in this study the activity of an identified set of uropod motor neurons during the fictive abdominal extension movement in the whole-animal preparation. Intracellular recordings from the dendritic branches of uropod motor neurons revealed that they were continuously excited during the fictive abdominal extension. The large fast motor neurons usually showed a sustained depolarization of the subthreshold magnitude. The small slow ones showed a suprathreshold sustained depolarization with spikes superimposed. Putative inhibitory motor neurons, on the other hand, showed a sustained hyperpolarization with their spontaneous spike discharge suppressed. The discrete synaptic potentials could hardly be distinguished and, instead, small fluctuations of the membrane potential were observed during the sustained depolarization of both the fast and slow motor neurons. Occasionally, large discrete synaptic potentials could be observed to be superimposed on the sustained depolarization. The occurring frequency of these synaptic potentials showed, however, no significant increase associated with the sustained depolarization. It hence seemed unlikely that these potentials were responsible for producing the sustained depolarization. Their amplitude during the sustained depolarization was smaller than that observed during the quiescent state. The sustained membrane potential change during the fictive abdominal movement was also observed in many neurons other than motor neurons, including local nonspiking interneurons and mechanosensory spiking interneurons. Both motor neurons and interneurons showed a decrease in their membrane resistance during the sustained membrane potential change. We concluded that the sustained depolarization of uropod motor neurons during the fictive abdominal extension was produced by the summation of small chemically transmitted postsynaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

The activities of new quinolones against 140 strains of methicillin-resistant Staphylococcus aureus were determined. From the relationship between the MICs of sparfloxacin and ciprofloxacin, fluoroquinolone-resistant S. aureus 6171 (MIC of sparfloxacin, 200 micrograms/ml; MIC of ciprofloxacin, 100 micrograms/ml) and fluoroquinolone-susceptible S. aureus FDA 209-P were selected for purification of the subunit A and B proteins of their DNA gyrases. The supercoiling activities of reconstituted ArBr (r, resistant) (from strain 6171) and ArBs (s, susceptible) gyrases were 40-fold more resistant to new quinolones than those of AsBs from FDA 209-P and AsBr gyrases. The 50% inhibitory doses of ciprofloxacin and sparfloxacin for AmBm (from mutant 19) and AmBs (m, moderately resistant) gyrases were 15- to 27-fold higher than those for AsBs and AsBm gyrases. These findings indicate that one of the resistance mechanisms of S. aureus against fluoroquinolones is a modification of the gyrase subunit A protein.

Electrical stimulation of mechanosensory afferents innervating hairs on the surface of the exopodite in crayfish Procambarus clarkii (Girard) elicited reciprocal activation of the antagonistic set of uropod motor neurones. The closer motor neurones were excited while the opener motor neurones were inhibited. This reciprocal pattern of activity in the uropod motor neurones was also produced by bath application of acetylcholine (ACh) and the cholinergic agonist, carbamylcholine (carbachol). The closing pattern of activity in the uropod motor neurones produced by sensory stimulation was completely eliminated by bath application of the ACh blocker, d-tubocurarine, though the spontaneous activity of the motor neurones was not affected significantly. Bath application of the acetylcholinesterase inhibitor, neostigmine, increased the amplitude and extended the time course of excitatory postsynaptic potentials (EPSPs) of ascending interneurones elicited by sensory stimulation. These results strongly suggest that synaptic transmission from mechanosensory afferents innervating hairs on the surface of the tailfan is cholinergic.

The antibacterial activities of tosufloxacin and other quinolones against and apparent uptakes of tosufloxacin and other quinolones by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium were studied. The hydrophobicity of tosufloxacin was nearly equal to that of ofloxacin or lower than those of sparfloxacin and nalidixic acid. OmpF- and OmpC-deficient E. coli and 40-kDa porin-deficient P. mirabilis mutants were twofold more susceptible to tosufloxacin and sparfloxacin but two- to fourfold less susceptible to other quinolones than their parent strains. In S. typhimurium lipopolysaccharide-deficient (rough) mutants, the differences in susceptibility to tosufloxacin were similar to those to sparfloxacin and nalidixic acid. The apparent uptake of tosufloxacin by intact cells was increased in porin-deficient mutants compared with that by their parent strain. These results suggest that the permeation route of tosufloxacin across the outer membrane is different from that of other fluoroquinolones and that tosufloxacin may permeate mainly through the nonporin pathway, presumably phospholipid bilayers. However, this characteristic is independent of the hydrophobicity of the molecule.

Pharmacological properties of excitatory synaptic transmission from mechanosensory afferents to an identifiable nonspiking interneuron of crayfish were studied by drug perfusion experiments using acetylcholine (ACh) agonists and antagonists. Application of carbachol, a general agonist of ACh, caused sustained depolarization of the interneuron and a decrease in the peak amplitude of its excitatory synaptic response to sensory stimulation on the soma side. Similar depolarization was observed during application of carbachol under the low-Ca2+, high-Mg2+ condition. The peak amplitude was also reduced by application of nicotine and tetramethylammonium, both of which also caused sustained depolarization of the inter-neuron. By contrast, perfusion of muscarinic agonists, muscarine, oxotremorine and pilocarpine, reduced the peak amplitude without affecting the membrane potential of the interneuron. Perfusion of nicotonic antagonists of ACh, d-tubocurarine and hexamethonium, caused reduction of the peak amplitude without any change in the membrane potential. A muscarinic antagonist atropine was also effective in blocking the synaptic transmission but at higher concentration than d-tubocurarine. The results suggest that the ACh receptors on the nonspiking interneuron belong to a previously characterized class of crustacean cholinergic receptors resembling the nicotinic subtype of vertebrates.

Voltage-dependent variability in the shape of synaptic responses of the LDS interneuron, an identified nonspiking cell of crayfish, to mechanosensory stimulation was studied using intracellular recording and current injection techniques. Stimulation of the sensory root ipsilateral to the interneuron soma evoked a large depolarizing synaptic response. Its peak amplitude was decreased and the time course was shortened when the LDS interneuron was depolarized by current injection. When the cell was hyperpolarized, the peak amplitude was increased and the time course was prolonged. Upon large hyperpolarization, however, the amplitude did not increase further while the time course showed a slight decrease. The dendritic membrane of the LDS interneuron was found to show an outward rectification upon depolarization and an inward rectification upon large hyperpolarization. Current injection experiments at varying membrane potentials revealed that the voltage-dependent changes in the shape of the synaptic response were based on an increase in membrane conductance due to the rectifying properties of the LDS interneuron. Stimulation of the contralateral root evoked a small depolarizing potential comprising an early excitatory response and a later inhibitory component. Its shape also varied depending on the membrane potential in a manner similar to that of the synaptic response evoked ipsilaterally.

Dendritic properties of uropod motoneurons and premotor nonspiking interneurons of crayfish have been studied using intradendritic recording and current injection. The input resistance of phasic motoneurons (5.20 ± 0.5 MO; mean ± standard error) measured by injecting constant hyperpolarizing current was significantly lower than that of tonic motoneurons (10.3 ± 2.6 MO; 0.02 < P < 0.05). The membrane time constant of phasic motoneurons (7.3 ± 0.9 ms) was also significantly shorter than that of tonic motoneurons (24.3 ± 2.5 ms; P < 0.001). Both types of motoneurons behaved linearly during hyperpolarization and sub-threshold depolarization. Nonspiking interneurons showed outward rectification upon depolarization. During hyperpolarization, their membrane behaved linearly and showed significantly higher input resistance (19.5 ± 2.5 MO) than phasic and tonic motoneurons (P < 0.001). Their membrane time constant (38.0 ± 5.7 ms) was significantly longer than that of phasic motoneurons (P < 0.001) but not than that of tonic motoneurons (P > 0.05). In response to intracellular injection of sinusoidally oscillating current, phasic motoneurons showed one or two spikes per depolarization period irrespective of oscillating frequency ranging from 1 to 16 Hz. Tonic motoneurons showed larger numbers of spikes per stimulus period at lower frequencies. Nonspiking interneurons also showed phase-locked effects on the motoneuron spike activity. The effective frequency range over which injected oscillating current could modulate motoneuron spike activity was similar for tonic motoneurons and nonspiking interneurons.

Summary 1.The uropod steering equilibrium response in crayfish is facilitated during the spontaneous abdominal posture movement. This facilitation could also be observed when the abdominal flexion or extension command interneuron was electrically stimulated at the circumesophageal commissure.2.One of the four known statocyst interneurons (C1) which transmit the position signal from the statocysts to the uropods was monitored while the animal was quiescent. It was activated by the extension command stimulation.3.The interneuron spike frequencies in response to a body tilt of 90° were not significantly different for the quiescent (21.0±1.1 imp/s) and the active (24.1±1.0) states. The spike frequency at 0° differed significantly for the quiescent (4.0±0.5) and the active (14.9±1.1) states.4.Simultaneous recording from the C1 interneuron and the uropod motoneurons showed that the tilt-increased activity of the C1 interneuron caused the steering response of uropod motoneurons only when the abdominal posture system was activated.5.We conclude that the facilitatory interaction between the steering and abdominal posture systems takes place between the interneurons and the uropod motoneurons inside the terminal abdominal ganglion. The statocyst interneurons are a controlling but not an initiating or a commanding element for the uropod steering movement.

1. Each abdominal ganglion of the crayfish contains peripheral inhibitors of the fast flexor muscles. These flexor inhibitors (FIs), which can effectively inhibit tension development in the tailflip powerstroke muscles, are excited by a delayed central pathway from the same giant axons which trigger escape (33). The FIs also received sensory input, which increases in efficacy in the more posterior segments (4), but until now neither the origin of the input nor its central pathways had been well described. We have used intracellular recording and staining techniques to investigate the afferent input onto the two telson flexor inhibitors (F16 and F17), which receive more powerful sensory input than any of their anterior homologs (4). 2. Both F16 and F17 showed a delayed (3.7 ms) compound postsynaptic potential (PSP), which peaked at long latency when any afferent nerve in the abdomen was stimulated. The amplitude of these slow PSPs waned rapidly with repeated stimulation at 1 Hz and was increased by hyperpolarization and decreased by depolarization of the FI. The PSPs are most likely to be mediated chemically, via polysynaptic pathways. 3. When any afferent nerve from the telson was stimulated, both telson FIs showed an additional fast-rising, short-latency (1.4 ms) PSP, which preceded the slow component. This fast component was not produced by afferent nerves innervating any region other than the telson. The fast PSPs of the two FIs were similar, but in F16 the fast component was always subthreshold, whereas in F17 it often elicited an impulse at short latency. 4. The amplitude of the fast component was not affected by changing the membrane potential of the FIs, suggesting electrical transmission. In spite of its short latency, the fast component is unlikely to be mediated monosynaptically, since it was variably present even in the same animal, and occlusion was observed when any two of the four telson nerves that evoked the response were stimulated simultaneously. 5. Although occlusion was seen among responses produced by stimulating afferents from any source, the responses summated linearly with the compound excitatory postsynaptic potential evoked in FI by the lateral giant escape command axons. Thus at least two separate suprathreshold pathways converge onto the telson FIs.

The crayfish ventral nerve cord contains two pairs of giant axons which are termed command axons for escape because impulses in either pair of cells trigger a complex series of neural events that culminates in a rapid flexion and extension of the abdomen, i.e. a ‘tailflip’ (Wine & Krasne, 1982). Each pair of axons triggers a specific trajectory of escape by virtue of differences in its intersegmental pattern of synapses with flexor motor neurones (Larimer, Eggleston, Masukawa & Kennedy, 1971 ; Wine & Krasne, 1972; Mittenthal & Wine, 1973; Miller, Hagiwara & Wine, 1985; Dumont & Wine, 1987b). However, while some of the flexor motor pathways are differentiated in a way that is consistent with the observed behaviour, a persistent puzzle has been the extraordinary degree of overlap in the output connections of the two kinds of giant axons to other portions of the flexor motor pathway. These overlapping connections should blur the distinction between the escape trajectories, and thus are inconsistent with the observed behaviour.

DNA gyrase from Staphylococcus aureus FDA 209P was partially purified by lysostaphin treatment, saturation with ammonium sulfate, and affinity chromatography on heparin-Sepharose and with a concentrator (Centricon 30). It was found to consist of two subunits: alpha and beta. The ability of new quinolone antibacterial agents such as norfloxacin, ofloxacin, and ciprofloxacin to inhibit DNA gyrase activity and cell growth was investigated. The inhibitory effects of the new quinolones against the activity of S. aureus DNA gyrase were in parallel with their antibacterial activities. The 50% inhibitory doses of norfloxacin, ofloxacin, and ciplofloxacin were 0.34, 0.31, and 0.24 micrograms/ml, respectively, while the 50% inhibitory doses of nalidixic acid and cinoxacin, which were less active against S. aureus FDA 209P, were 100 micrograms/ml or more.

When the crayfish Procambarus is rolled with legs not upon a substratum, uropod opener muscles on the lifted side are activated in co-contraction whereas antagonistic closer muscles on the same side are all relaxed simultaneously. The closers are activated and the openers are relaxed on the lowered side. This reciprocal pattern is also observed in the motor neurone activity: the contraction of opener muscles on the lifted side and closer muscles on the lowered side is caused by an increase in the activity of excitatory motor neurones innervating these muscles, whereas the relaxation of their antagonists on each side is caused by a decrease in the activity of excitatory motor neurones innervating them. Deafferentation by cutting all roots of the terminal ganglion has no significant effect on the steering pattern. The decrease in the excitatory motor neurone activity during steering was found to be due to an increase in the inhibitory input to the motor neurones. During body rolling, the statocyst receptors on the lifted side increase their activity while those on the lowered side decrease it (Takahata & Hisada, 1979). We conclude that the opener motor neurones receive excitation and inhibition respectively from the ipsilateral and the contralateral statocyst, whereas the closer motor neurones receive excitation and inhibition respectively from the contralateral and ipsilateral statocyst. From these results, the connections between the motor neurones and the identified statocyst interneurones were deduced. The normal, bilaterally organized steering pattern of the uropod muscle activity seems to be produced by the statocysts of both sides, whose information is mediated by a bilateral set of interneurones having different connections to individual motor neurones.

The activities of T-1982 (sodium 7 beta-[(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazine-carboxamido)-3-hydroxybutanamido]-7 alpha-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylate) against various gram-positive and gram-negative bacteria were compare with those of cefmetazole, cefoxitin, cefazolin, and cefoperazone. T-1982 was active against both gram-positive and gram-negative bacteria, including genera resistant to the other cephalosporins. T-1982 exhibited greater activity than did cefmetazole, cefoxitin, cefazolin, or cefoperazone against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Serratia marcescens and was also highly active against Bacteroides fragilis. T-1982 was as stable to various beta-lactamases as were cefmetazole and cefoxitin. The therapeutic activities of T-1982 in mice experimentally infected with various gram-negative bacteria were superior to those of cefmetazole, cefoxitin, cefazolin, and cefoperazone.

We report on the characterization of an AC-coupled, double-sided silicon strip detector, with fast binary readout electronics, in a pion beam before and after proton irradiation. The proton irradiation was non-uniform and to increase the damage the detector was heated to accelerate the anti-annealing. The effective radiation level was about 1/spl times/10/sup 14/ p/cm/sup 2/. Both the bias voltage of the detector and the threshold of the discriminator of the binary readout electronics were varied, and the efficiencies were determined. The irradiated detector clearly shows the effect of bulk inversion. The binary system proved to be efficient well below the full depletion voltage on the p-n junction side. Due to the highly non-uniform irradiation, the depletion voltage changes from close to zero to about 120 V along a single strip, but the detector appears to work without any noticeable failures.

T-3761, a new quinolone derivative, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.20 to 100 micrograms/ml against gram-positive bacteria, including members of the genera Staphylococcus, Streptococcus, and Enterococcus; 0.025 to 3.13 micrograms/ml against gram-negative bacteria, including members of the family Enterobacteriaceae and the genus Haemophilus; 0.05 to 50 micrograms/ml against glucose nonfermenters, including members of the genera Pseudomonas, Xanthomonas, Acinetobacter, Alcaligenes, and Moraxella; 0.025 micrograms/ml against Legionella spp.; and 6.25 to 25 micrograms/ml against anaerobes, including Bacteroides fragilis, Clostridium difficile, and Peptostreptococcus spp. The in vitro activity of T-3761 against these clinical isolates was comparable to or 2- to 32-fold greater than those of ofloxacin and norfloxacin and 2- to 16-fold less and 1- to 8-fold greater than those of ciprofloxacin and tosulfoxacin, respectively. When administered orally, T-3761 showed good efficacy in mice against systemic, pulmonary, and urinary tract infections with gram-positive and gram-negative bacteria, including quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa. The in vivo activity of T-3761 was comparable to or greater than those of ofloxacin, ciprofloxacin, norfloxacin, and tosufloxacin against most infection models in mice. The activities of T-3761 were lower than those of tosufloxacin against gram-positive bacterial systemic and pulmonary infections in mice but not against infections with methicillin-resistant Staphylococcus aureus. The activities of T-3761 against systemic quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa infections in mice were 2- to 14-fold greater than those of the reference agents.

The mutations in the quinolone resistance-determining region of the gyrA gene from clinical isolates of Pseudomonas aeruginosa were determined by DNA sequencing. The strains were isolated in 1989 and 1993. No mutations were detected in the clinical isolates in 1989, while five types of mutations were identified in the isolates in 1993. These mutations were as follows: group 1, a Thr residue to an Ile residue at position 83 (Thr-83-Ile); group 2, Asp-87-Asn; group 3, Thr-83-Ile and Asp-87-Gly; group 4, Thr-83-Ile and Asp-87-Asn; group 5, Thr-83-Ile and Asp-87-His. Three types of double mutations (groups 3, 4, and 5) have not been described previously. These mutations were homologous to the Ser-83-Leu, Asp-87-Asn, and Asp-87-Gly changes observed in Escherichia coli. Thus, DNA gyrase A subunit mutations are implicated in resistance to quinolones in P. aeruginosa as well as E. coli.

The MIC of norfloxacin for the norA-disrupted mutant termed RDN1, obtained from quinolone-susceptible Staphylococcus aureus RN4220, was eightfold lower than that for RN4220. The increase in susceptibility was related to an increase of drug accumulation by RDN1. These results indicate that NorA plays an important role in the susceptibility of quinolone-susceptible S. aureus to selected quinolones.