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Biomedical subjects

N Furuya

Publications and source records attributed to N Furuya.

At least 19 recordsLinked to original sources

Neurotransmitters in the vestibular commissural system of the cat.

The present study focused on the transmitters that control the vestibular neural activity and, in particular, that regulate commissural inhibition. Extracellular spikes of a single vestibular neuron were recorded in decerebrate cats. The seven barrels of the electrode, with the exception of the center barrel, were filled with transmitter candidates and their specific antagonists, while the center barrel was filled with 2 M NaCl for extracellular recording. After isolation of a type 1 neuron, chemicals were iontophoretically applied to examine their effects on its activity. The results were as follows: (1) GABA and glycine markedly decreased spontaneous firing of the neurons, while serotonin did not affect their activity. (2) Bicuculline abolished the inhibitory effects of GABA on the neurons. (3) Strychine abolished the effects of glycine. (4) Commissural inhibition induced by electrical stimulation of the contralateral labyrinth was not abolished by strychine but was abolished by bicuculline. We conclude that (1) vestibular type 1 neurons are controlled by GABAergic and glycinergic but not serotoninergic neurons, and (2) commissural inhibition is activated by the GABAA receptor, but not by the GABAB receptor.

Animals

[Role of capsular polysaccharide and lipopolysaccharide of Klebsiella pneumoniae in experimental mice pneumonia model].

In this study, role of capsular polysaccharide (CPS) and lipopolysaccharide (LPS) of Klebsiella pneumoniae was investigated in experimental mice pneumonia model. Inoculation with K. pneumoniae mucoid strain DT-S into mice lung induced expansive, voluminous lethal pneumonia characterized with thickening of the alveolar septa caused by infiltration of inflammatory cell and packing of bacteria within alveolar spaces. On the other hand, mice lung inoculated with K. pneumoniae DT-X, which was non-mucoid mutant isolated from DT-S during natural passage, showed infiltration of inflammatory cell into alveolar spaces but there was no death of mice during the course of this pneumonia. Inoculation of CPS 100 micrograms of DT-S strain into mice lung induced lesser extent of accumulation of inflammatory cell than that of LPS 4 micrograms of this strain. Stimulation of alveolar and peritoneal macrophage with CPS, even at a concentration of 100 micrograms/ml, induced weaker Interleukin-1 (IL-1) activity than stimulation with LPS 4 micrograms/ml. These results suggest that since CPS of K. pneumoniae DT-S encapsulate bacteria including LPS, CPS may inhibit chemotaxis of inflammatory cell and IL-1 production of macrophage to be induced by LPS during course of pneumonia. It is speculated that existence of CPS have important role in modulating host response to bacterial LPS, and this effect of CPS may be related with difference of pathological findings of lung and lethality between K. pneumoniae DT-S and DT-X.

Animals

[Effect of azithromycin on human serum sensitivity of Pseudomonas aeruginosa].

We examined the effect of azithromycin (AZM), a 15-membered azalide newly synthesized from erythromycin (EM), on serum sensitivity of 6 strains of Pseudomonas aeruginosa. Incubation for 48 h on agar with EM 12 micrograms/ml or AZM 1.6 micrograms/ml induced increased serum sensitivity in 2 of 6 strains (S-6, PA-103), but there were no changes in any strains with josamycin (JM) 12 micrograms/ml. Although EM 12 micrograms/ml induced increased serum sensitivity of S-6 after more than 36 h incubation, AZM 1.6 micrograms/ml induced increased serum sensitivity of this strain at 12 h incubation. AZM 0.8 microgram/ml (1/62.5 MIC) showed more potent activity to enhance serum sensitivity of S-6 than that of EM 12 micrograms/ml (1/8 MIC) after 48 h incubation. P. aeruginosa S-6 incubated with EM 12 micrograms/ml or AZM 1.6 micrograms/ml for 48 h was less hydrophobic than that of control bacteria, but there was little change in the hydrophobicity of the strain incubated with JM 12 micrograms/ml. These results show that AZM has more potent activity to enhance serum sensitivity of P. aeruginosa than that of EM. Since decrease of cell surface hydrophobicity of P. aeruginosa S-6 was correlated with increased serum sensitivity, EM and AZM may induce enhanced serum sensitivity by changing cell surface structure of P. aeruginosa.

Azithromycin

Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice.

We induced endogenous Pseudomonas aeruginosa bacteremia by administering cyclophosphamide and ampicillin to specific pathogen-free mice fed P. aeruginosa. Using this model, we evaluated the efficacy of erythromycin lactobionate (EML) in treating P. aeruginosa bacteremia. Treatment with EML at 50 and 100 mg/kg of body weight per day twice a day for 14 days significantly increased the survival rate. The most effective dose was 100 mg/kg/day, with a survival rate of 80% compared with a 20% survival rate in the control. However, the administration of EML at 500 mg/kg/day rather decreased the survival rate. In a model of intravenous infection, treatment with EML at 100 mg/kg/day twice a day for 7 days before the bacterial challenge also enhanced the survival rate. EML levels in serum, liver, and stool were apparently lower than the MIC (512 micrograms/ml). These observations suggest that EML is effective against P. aeruginosa bacteremia despite a lack of specific activity for this pathogen. Although the protective mechanism is still unclear, it is possible that a subinhibitory level of EML may affect the virulence of P. aeruginosa and enhance the host defense system.

Animals

Potential effects of erythromycin on host defense systems and virulence of Pseudomonas aeruginosa.

We evaluated several potential effects of erythromycin (EM) on host defense systems and the virulence of Pseudomonas aeruginosa. Peritoneal macrophages obtained from mice given 250 mg of EM per kg of body weight for 7 days by the intraperitoneal, intravenous, subcutaneous, or oral route produced significantly greater amounts of thymocyte-activating factors. These data suggest that EM enhances the in vivo production of cytokines, such as interleukins 1 and 6. Treatment of P. aeruginosa D4 with subinhibitory concentrations of EM enhanced the association of bacteria with murine Kupffer cells in vitro and increased bacterial clearance from the blood in mice. EM suppressed the in vitro production of exotoxin A, total protease, elastase, and phospholipase C by P. aeruginosa D4; exotoxin A production by P. aeruginosa PA-103; and total protease production by P. aeruginosa B16 and PAO1 in a generally dose-dependent manner. These data demonstrate that EM produces various effects in addition to its direct antimicrobial activity, suggesting that it has potential as an immunomodulator or bacterial virulence-suppressing agent against P. aeruginosa and other infections.

Adjuvants, Immunologic

[Effect of macrolide antibiotics on human serum-bactericidal sensitivity of Pseudomonas aeruginosa S-6].

It is well known that long-term administration of erythromycin (EM) at a small dose is effective for persistent infections with Pseudomonas aeruginosa in diffuse panbronchiolitis or chronic bronchitis patients. Since EM is less active against P. aeruginosa in vitro, we have been interested in the mechanisms of clinical efficacy of EM in these patients. This study examines the effect of macrolide antibiotics on human serum-bactericidal sensitivity of P. aeruginosa S-6, clinically isolated from the patient with respiratory tract infection. A significant increase in serum-bactericidal sensitivity of P. aeruginosa S-6 was observed on agar containing EM of 10 micrograms/ml after incubation for 36-60 hours (p less than 0.05). The enhancement of serum sensitivity of P. aeruginosa S-6 was apparently observed even at a concentration of EM 1.5 micrograms/ml after the 48 hours incubation (p less than 0.01). Of other macrolide antibiotics used, clarithromycin (CAM) also increased the serum-bactericidal sensitivity of P. aeruginosa S-6 as well as EM, however no change in the sensitivity was found with kitasamycin, josamycin, rokitamycin and oleandomycin. The results suggest that the change of serum-bactericidal sensitivity of P. aeruginosa induced by EM or CAM may, in part, contribute to the clinical efficacy of these antibiotics against persistent pulmonary P. aeruginosa infections.

Anti-Bacterial Agents

Role of bacterial association with Kupffer cells in occurrence of endogenous systemic bacteremia.

Bacteremia in immunocompromised hosts often arises from their endogenous intestinal flora. We produced experimental endogenous bacteremia by administering cyclophosphamide and ampicillin to conventional and specific-pathogen-free mice. The frequencies of bacteremia and mortality in the conventional mice were significantly higher than for the specific-pathogen-free mice. Pseudomonas aeruginosa was the major pathogen causing systemic bacteremia in conventional mice and was associated with a high mortality rate. Morganella morganii caused systemic bacteremia in both conventional and specific-pathogen-free mice. In contrast, Escherichia coli, enterococci, or other species most often caused portal bacteremia only. To determine the mechanism of occurrence of systemic bacteremia, we investigated bacterial blood clearance in mice and association with murine Kupffer cells, using several bacterial strains isolated from mice with bacteremia. Blood clearance rates and the abilities of isolated Kupffer cells to associate with bacteria were significantly greater for the organisms causing portal bacteremia than for those causing systemic bacteremia. There were no significant differences between the blood clearance rates in carrageenan-treated mice and that in normal mice. Moreover, association at 4 degrees C was not different from that at 37 degrees C. The results suggest that blood clearance of bacteria reflects bacterial adherence to Kupffer cells and that the resistance of bacteria to association with Kupffer cells plays an important role in the occurrence of overwhelming systemic bacteremia in this animal model.

Agglutination

Determination of the nick site at oriT of IncI1 plasmid R64: global similarity of oriT structures of IncI1 and IncP plasmids.

The nick site at the origin of transfer, oriT, of IncI1 plasmid R64 was determined. A site-specific and strand-specific cleavage of the phosphodiester bond was introduced during relaxation of the oriT plasmid DNA. Cleavage occurred between 2'-deoxyguanosine and thymidine residues, within the 44-bp oriT core sequence. The nick site was located 8 bp from the 17-bp repeat. A protein appeared to be associated with the cleaved DNA strand at the oriT site following relaxation. This protein was observed to bind to the 5' end of the cleaved strand, since the 5'-phosphate of the cleaved strand was resistant to the phosphate exchange reaction by polynucleotide kinase. In contrast, the 3' end of the cleaved strand appeared free, since it was susceptible to primer extension by DNA polymerase I. The global similarity of the oriT structures of IncI1 and IncP plasmids is discussed.

Base Sequence

Nucleotide sequence and functions of the oriT operon in IncI1 plasmid R64.

Two transfer genes of IncI1 plasmid R64, tentatively designated nikA and nikB, were cloned and sequenced. They are located adjacent to the origin of transfer (oriT) and appear to be organized into an operon, which we call the oriT operon. On the basis of the DNA sequence, nikA and nikB were concluded to encode proteins with 110 and 899 amino acid residues, respectively. Complementation analysis indicated that these two genes are indispensable for the transfer of R64 but are not required for the mobilization of ColE1. By the maxicell procedure, the product of nikA was found to be a 15-kDa protein. On treating a cleared lysate prepared from cells harboring a plasmid containing oriT, nikA, and nikB with sodium dodecyl sulfate or proteinase K, superhelical plasmid DNA in the cleared lysate was converted to an open circular form (relaxation). Relaxation of plasmid DNA was found to require the oriT sequence in cis and the nikA and nikB sequences in trans. It would thus follow that the products of nikA and nikB genes form a relaxation complex with plasmid DNA at the oriT site.

Amino Acid Sequence

[Metabolic study on chondroitin sulfates in rabbits].

The metabolic studies on three types of chondroitin sulfates in rabbits were performed. The analyses of chondroitin sulfates gave the following results concerning their metabolic behavior. 1) Desulfation of chondroitin sulfates on GalNAc C6 position was observed more clearly after the administration of low molecular weight chondroitin sulfate (molecular weight, 6000 and 16,000) than after that of high molecular weight one (molecular weight, 50,000). 2) The disappearance velocities of the administered low molecular weight chondroitin sulfates in the blood and those of excretion into the urine were faster than those of high molecular weight one. 3) Intact chondroitin sulfates were excreted into the urine after the administration of low molecular weight chondroitin sulfates, while chondroitin sulfates having more than 30000 molecular weight were not detected in the collected urine after the administration of high molecular weight one.

Animals

Effects of serotonin, GABA and glycine on the activity of pause neurons during vestibular nystagmus in the cat.

Pause neurons (PNs), found in the pontine raphe nuclei, are important in the regulation of fast eye movements. The present study focuses on transmitters regulating the activity of the PNs. Extracellular spikes of single PNs and ocular motor nerve discharges were simultaneously recorded during horizontal vestibular nystagmus in the alert cat. Several transmitter candidates were iontophoretically applied, while methysergide, a serotonin antagonist, was administered both systemically and topically. The following data supported the conclusion that PNs are probably under the control of two different types of neurons, and the firing of PNs may be caused partly by GABAergic, but not by glycinergic neurons: 1) serotonin markedly decreased the spontaneous firing of the PNs; 2) methysergide abolished the inhibitory effect of serotonin on the PN firing; however, a pause pattern was maintained under this condition; 3) GABA moderately suppressed the firing but only in 25% of PNs; and 4) glycine hardly changed the PN firing in any case examined.

Animals

Neurotransmitters regulating vestibular commissural inhibition in the cat.

The present study focuses on the transmitters which control the vestibular neural activity and, in particular, those which regulate commissural inhibition. Extracellular spike recordings were taken from single vestibular neurons of decerebrate cats. Seven-barreled electrodes were used. The barrels, except for the central one, were filled with several transmitter candidates and their specific inhibitors. After isolation of a type I neuron, the chemicals were iontophoretically applied to examine their effects on the activity of the neuron. The results were as follows: i) GABA and glycine markedly decreased spontaneous firing of the neurons, while serotonin did not change the activity. ii) Bicuculline abolished the inhibitory effects of GABA on the neurons. iii) Strychnine also abolished the effects of glycine, iv) Commissural inhibition caused by electrical stimulation of the contralateral labyrinth was not abolished by the application of strychnine but was abolished by bicuculline. We concluded that 1) vestibular type 1 neurons are controlled by GABAergic and glycinergic neurons, and that 2) the commissural inhibition is activated by the GABAA receptor, but not by the GABAB receptor.

Animals

Computer analysis of the optokinetic pattern test in acoustic tumors, brain stem and cerebellar lesions. Slow and fast phase velocities of optokinetic nystagmus.

Optokinetic pattern (OKP) abnormalities in 36 patients with infratentorial lesions were analyzed by microcomputer (7T18 Nihondenki-Sanei). The parameters used for analysis consisted of slow phase velocity (S-VEL) and fast phase velocity (F-VEL) in optokinetic nystagmus. In 16 patients with acoustic tumors, S-VELs were normal or borderline when the tumors were less than 2 cm in diameter, but when the tumors were more than 2 cm, S-VELs were severely impaired. In 20 patients with brain stem and/or cerebellar lesions, S-VELs were abnormal in all the patients with the exception of 3. F-VEL abnormalities were seen in only 5 patients with brain stem lesions, especially pontine lesions. These findings suggest that S-VEL is a sensitive indicator of infratentorial lesions and F-VEL an important indicator of pontine lesions.

Brain Diseases

Computer analysis of optokinetic pattern test for patients with localized lesions of unilateral frontal eye fields.

Four patients with localized lesions of the left frontal eye field as demonstrated at autopsy or MRI were studied. Their electronystagmography (ENG) recordings, which were induced by optokinetic stimulus, were analyzed by computer. Four factors were calculated by the ENG analyzing program. We conclude that the asymmetry of OKP in patients with localized lesions of the unilateral frontal eye fields is primarily caused by impaired S-VEL and F-VEL of the contralateral OKN compared with the side of the frontal eye field lesion.

Adult

Slow and fast phase velocities of optokinetic nystagmus induced by the optokinetic pattern test in infratentorial lesions.

Optokinetic pattern (OKP) abnormalities in 36 patients with infratentorial lesions confirmed by CT or MRI were analyzed by microcomputer. The computer analysis system enabled the OKP data to be changed to digital data consisting of the slow phase velocity (S-VEL) and the fast phase velocity (F-VEL) in optikinetic nystagmus. In 16 patients with acoustic tumors. S-VELs were normal or borderline when the tumors were less than 2 cm in diameter, but when the tumors were more than 2 cm. S-VELs were severely impaired. F-VEL abnormalities were not seen in our study except in one patient. In 20 patients with brain stem and/or cerebellar lesions, S-VELs were abnormal in all the patients with the exception of 3. There was no significant difference in S-VEL between the group with brain stem lesions and that with cerebellar lesions. F-VEL abnormalities were seen in only 4 patients with brain stem lesions, especially pontine lesions. These findings suggest that S-VEL is a sensitive indicator for infratentorial lesions and F-VEL an important indicator for pontine lesions.

Adolescent

Breathing patterns during sleep in stable asthmatic children.

Breathing patterns during sleep at night were studied in 15 asymptomatic asthmatic children and 11 nonasthmatic controls using impedance pneumography. Inspiratory time (TI), expiratory time (TE) and expiratory time/inspiratory time ratio (TE/TI) were used as the indices of breathing patterns. In the daytime, TI, TE and TE/TI, showed no significant differences between asthmatics and controls. During nocturnal sleep, TE and TE/TI increased significantly in the asthmatics compared with the value during daytime, while these values showed only a small variation overnight in the controls. TI showed no significant changes through the night in either the asthmatics and the controls. The results of this study indicate that the stable asthmatic children had abnormal breathing patterns during nocturnal sleep.

Adolescent