Biomedical subjects

M Kitabatake

Publications and source records attributed to M Kitabatake.

At least 19 recordsLinked to original sources

PubMed1997

Continuous low-dose NO inhalation does not prevent monocrotaline-induced pulmonary hypertension in rats.

We determined whether vasodilator doses of inhaled nitric oxide (NO) prevented the progression of pulmonary hypertension (PH) and vascular changes in monocrotaline-induced PH. Short-term NO inhalation in rats 3 wk after the injection of monocrotaline reduced mean pulmonary artery pressure (PAP) from 30.7 +/- 2.2 (SE) to 26.4 +/- 1.4 mmHg at 10 parts per million (ppm) and from 30.2 +/- 1.3 to 25.8 +/- 1.4 mmHg at 40 ppm. There were no differences among rats exposed to air only and rats exposed to 10 ppm of NO for 19 days after a single subcutaneous injection of monocrotaline, in mean PAP (34.3 +/- 1.9 mmHg air vs. 32.8 +/- 1.4 mmHg NO), right ventricular hypertrophy (RVH), medial wall thickness (MWT) of muscular arteries, and the percentage of muscularized arteries at alveolar wall (%AW) and duct (%AD) level. Additional groups exposed to air only and 40 ppm of NO for 19 days again showed no difference in mean PAP, RVH, MWT, and %AD, except that this dose slightly reduced %AW (60.6 +/- 3.4% air vs. 46.9 +/- 5.2% NO, P = 0.04). Urine nitrate (NO3) level was higher in rats that had inhaled NO. In contrast to chronic hypoxic PH, vasodilator doses of NO inhalation did not prevent the development of PH in this malignant form of experimental PH.

Administration, Inhalation↗

PubMed1996

Genetic analysis of functional connectivity between substrate recognition domains of Escherichia coli glutaminyl-tRNA synthetase.

It has previously been shown that the single mutation E222K in glutaminyl-tRNA synthetase (GlnRS) confers a temperature-sensitive phenotype on Escherichia coli. Here we report the isolation of a pseudorevertant of this mutation, E222K/C171G, which was subsequently employed to investigate the role of these residues in substrate discrimination. The three-dimensional structure of the tRNA(Gln): GlnRS: ATP ternary complex revealed that both E222 and C171 are close to regions of the protein involved in interactions with both the acceptor stem and the 3' end of tRNA(Gln). The potential involvement of E222 and C171 in these interactions was confirmed by the observation that GlnRS-E222K was able to mischarge supF tRNA(Tyr) considerably more efficiently than the wild-type enzyme, whereas GlnRS-E222K/C171G could not. These differences in substrate specificity also extended to anticodon recognition, with the double mutant able to distinguish supE tRNA(CUA)(Gln) from tRNA2(Gln) considerably more efficiently than GlnRS E222K. Furthermore, GlnRS-E222K was found to have a 15-fold higher K(m) for glutamine than the wild-type enzyme, whereas the double mutant only showed a 7-fold increase. These results indicate that the C171G mutation improves both substrate discrimination and recognition at three domains in GlnRS-E222K, confirming recent proposals that there are extensive interactions between the active site and regions of the enzyme involved in tRNA binding.

Adenosine Triphosphate↗

PubMed1996

Cloning of a gene from Escherichia coli that confers resistance to fosmidomycin as a consequence of amplification.

A gene conferring resistance to fosmidomycin (Fs) was cloned from the gene pool of a wild-type strain of Escherichia coli. The cloned DNA fragment was sequenced and shown to encode a putative polypeptide of 406 amino acids (aa) with a molecular weight of 43303. The gene mapped at 10.9 min on the E. coli chromosome and was designated fsr (fosmidomycin resistance). Maxicell analysis revealed that the Fsr protein migrated in sodium dodecyl sulfate-polyacrylamide-gel electrophoresis as a broad band of 35 kDa. A comparison between the aa sequence of Fsr and sequences in a protein database revealed 18% homology to the bacterial drug-export proteins that mediate resistance to tetracycline and chloramphenicol. Hydropathy analysis of the Fsr protein revealed twelve putative transmembrane segments. The degree of FsR of transformants depended on the number of copies of the plasmid that contained fsr. The levels of ubiquinone-8 and undecaprenyl phosphate in cells that harbored a high-copy-number plasmid that included fsr were almost the same as those in the cells without the plasmid. These results suggest that Fsr does not have any direct effect on the biosynthesis of isoprenoid in E. coli, and that the mechanism for FsR involves the efflux of the drug by a process that is facilitated by Fsr.

Amino Acid Sequence↗

PubMed1996

10Sa RNA is associated with 70S ribosome particles in Escherichia coli.

The intracellular distribution of 10Sa RNA in Escherichia coli was investigated in cell extracts. Northern hybridization revealed that a large fraction of 10Sa RNA cosediments with 70S ribosomes. When 70S ribosomes were dissociated into 50S and 30S subunits in the presence of low levels of Mg2+ ions, almost all of the 10Sa RNA disappeared from both subunits. The extent of the association of the 10Sa RNA with ribosomes was much enhanced during the growth phase of the cells. These results suggest the possibility that 10Sa RNA might function on the ribosomes in E. coli cells.

Autoradiography↗

PubMed1996

10Sa RNA complements the temperature-sensitive phenotype caused by a mutation in the phosphoribosyl pyrophosphate synthetase (prs) gene in Escherichia coli.

From Escherichia coli cells with a deletion in the ssrA gene that encodes 10Sa RNA after treatment with a mutagen, we isolated two temperature-sensitive mutants, which we designated TS15 and TS101. The temperature-sensitive (ts) phenotype of the mutants could be overcome by introduction of the wild-type ssrA gene but not by the mutants of ssrA. By a complementation test using Kohara's mini-set of clones and by subcloning of a fragment from the phage clone 246, we found that both mutations were in the prs gene that encodes phosphoribosyl pyrophosphate synthetase. Sequencing of the mutant prs gene of TS101 showed that residues 215, cysteine, in the encoded protein had been changed to tyrosine. That such a mutant exists suggests that 10Sa RNA associate with the prs gene product in a functional way.

Escherichia coli↗

PubMed1996

[Depression symptoms among Chinese students in Japan].

The mental health of foreigners in Japan, which shows a prominent increase in number recently was studied. A major group of these foreigners are Korean and Chinese, as their countries and Japan historically had a close relationship. The Chinese population has shown large increases, quadrupling over a period of 10 years. This population is characterized by purpose of residence; with most of them visiting Japan to study. Using the Beck Depression Inventory (BDI) self rating scale, we examined depression symptoms among two groups of Chinese students studying in Japan; 71 students of Mie university (MU) and 90 students of Japanese language schools (JLS) in Mie prefecture. BDI examination revealed that 28.9% (mild; 22.2%, moderate; 3.3%, severe; 3.3%) of Chinese JLS students and 23.9% (mild; 22.5%, severe; 1.4%) of Chinese MU students were depressed. Chinese JLS students showed significantly higher total BDI scores than Chinese MU students (p < 0.05). BDI scores of item D (lack of satisfaction), J (crying spells) and S (weight loss) were also significantly elevated in Chinese JLS students (D: p < 0.01, J: p < 0.05, S: p < 0.01). These results suggest that Chinese JLS students experience more stress than Chinese MU students.

Adult↗

PubMed1995

Effects of exposure to NO2 or SO2 on bronchopulmonary reaction induced by Candida albicans in guinea pigs.

The effects of NO2 or SO2 on the bronchopulmonary reactions induced by Candida albicans in guinea pigs were evaluated. Thirty-six guinea pigs (3 groups of 12 animals each) were sensitized with intraperitoneal injection of 10 mg of C. albicans, given twice. Two groups of animals were exposed to about 5 ppm of NO2 or SO2 for 4 h/d, 5 d/wk; this exposure was conducted a total of 30 times during the study. The third group served as the control and was not exposed to these pollutants. Two weeks after the second sensitization, all the animals were subjected to inhalation exposure to C. albicans. For 42 h after the antigen challenge, the respiratory rates and expiration/inspiration ratios of the animals were automatically monitored. The number of animals showing tachypnea was significantly higher in the NO2 exposure group than in the control from 15 h after antigen challenge. In the SO2 exposure group, the number of animals showing prolonged expiration or prolonged inspiration, or both, was significantly higher than that in the control group, and the symptoms were observed from approximately 15 h after antigen challenge. These findings showed that delayed-type dyspneic symptoms in guinea pigs were increased by exposure to NO2 or SO2, although the symptoms and degree of dyspnea were different for the two gases.

Administration, Inhalation↗

PubMed1995

Seasonal mood variation among Japanese residents of Stockholm.

Depressive symptoms estimated by the Beck Depression Inventory (BDI) were examined in winter and summer in a total of 242 Japanese adults staying less than 2 years or longer than 10 years in Stockholm, where the length of daylight changes dramatically throughout the winter and summer seasons. In spite of the difference in the period of residency, both groups of subjects showed more mental and somatic depressive symptoms in the winter than in the summer. Moreover, the winter BDI score of long stayers was significantly higher than that of short stayers. Accordingly, our results suggest that, although seasonal mood variation is essentially produced by a chronobiological factor, Swedish lifestyle to which long stayers have been accustomed also influences the seasonal mood variation.

Acclimatization↗

PubMed1995

[Trends of air pollution versus those of consultation rate and mortality rate for bronchial asthma in individuals aged 40 years and above in the Yokkaichi region].

We performed correlation analysis on the relationship between changes in air pollution and the consultation rate for bronchial asthma in the Yokkaichi region, taking effects of various socioeconomic factors into consideration. The effects of changes in air pollution on the mortality rate due to bronchial asthma were also evaluated. 1. Evaluation of annual changes in the simple correlation coefficient between the consultation rate and the concentration of each pollutant showed no significant correlation with a decrease in the air pollutant concentration in the age group less than 10 years old. However, in the middle-advanced male and female groups aged 40 years and above, the influence of past air pollution still remained. In addition, the partial correlation coefficients between the consultation rate for bronchial asthma and the degree of pollution, socioeconomic factors, and the rate of heavy smokers were calculated. A significant correlation was observed between the consultation rate for the females in each age group and the rate of patients receiving public assistance. 2. The mortality rate due to bronchial asthma in the polluted area increased rapidly with a time lag of several years after the peak of air pollution but decreased gradually thereafter. Presently, the mortality rate in the polluted area is similar to that in the non-polluted (control) area. 3. The mean age of death due to bronchial asthma was elevated because of a decrease in the deaths of those aged less than 60 years. As a result, the difference in the mean age of death due to bronchial asthma between the polluted area and the control area disappeared. With the recent remarkable alleviation of air pollution, the consultation rate and mortality rate due to bronchial asthma have decreased considerably. However, differences are still observed compared with the control area in some age levels so that continuation of monitoring of air pollution as well as consultation and mortality rates is considered necessary.

Adult↗

PubMed1995

Effects of various post-treatment by phenylmethylsulfonyl fluoride on delayed neurotoxicity induced by leptophos.

Delayed neurotoxicity induced by leptophos, an organophosphorus insecticide, was intensified in hens when phenylmethylsulfonyl fluoride (PMSF) at dose of 30, 60, and 120 mg/kg body weight was administered at different time intervals (24 hr, 3 days, and 5 days) for each dose of PMSF after the hens were exposed to 30 mg/kg (i.v.) of leptophos. The scores for organophosphorus-induced delayed neuropathy (OPIDN) in all groups treated with 120 mg/kg PMSF were significantly higher than those in the group treated with leptophos only (P<0.05 or P<0.01) and the initial signs of OPIDN appeared 2 or 3 days earlier in the former groups than in the latter group. Further, the greater the PMSF post-treatment dose, the more severe were the signs of OPIDN. These findings indicate that post-treatment with PMSF promotes leptophos-induced OPIDN and reduces the period to OPIDN onset. We also examined the effects of various time intervals between PMSF administration and exposure to leptophos on the development of OPIDN. The OPIDN scores in the two groups of hen treated with PMSF on days 3 and 5 after leptophos exposure were high, especially the score of the 5 days treated group became significantly higher on the 18th and 19th day after leptophos administration than even that of the 24 hr treated group with PMSF (P<0.05). These findings suggest that variations in both the dose of PMSF and the time intervals of PMSF post-treatment may affect the delayed neurotoxicity induced by leptophos. Moreover, these results also indicate that PMSF should not be used for either the treatment or the prevention of OPIDN.

Animals↗

PubMed1995

[Remission and recurrence of chronic obstructive lung disease in air pollution caused lung disease patients in the Yokkaichi area].

A study was conducted of patients covered by National Health Insurance (NHI) with chronic obstructive lung diseases legally-recognized as being caused by air pollution (Group A) and those not legally-recognized as air pollution caused (Group B) in the Yokkaichi area. Records of medical examinations (medical fee NHI statement), were examined, focusing on recurrence and remission. Over all incidence of recurrence after remission in asthmatic bronchitis and bronchial asthma conditions was 25% in Group A and 18% in Group B patients although with differences observed in different age groups. Approximately 50%-70% of the recurrence occurred within 3 years, and this incidence decreased approximately in proportion to time elapsed. Total remission rates for patients who had remission without recurrence and those who had remission after recurrence of bronchial asthma was approximately 39% in Group A and about 77% in Group B.

Adolescent↗

PubMed1994

A tRNA-like structure is present in 10Sa RNA, a small stable RNA from Escherichia coli.

We have determined that 10Sa RNA (one of the small stable RNAs found in Escherichia coli) has an interesting structural feature: the 5' end and the 3' end of 10Sa RNA can be arranged in a structure that is equivalent to a half-molecule (acceptor stem and TFC stem-loop) of alanine tRNA of E. coli. Primer-extension analysis of 10Sa RNA extracted from a bacterial mutant with temperature-sensitive RNase P function revealed that the precursor to 10Sa RNA (pre-10Sa RNA) is folded into a pre-tRNA-like structure in vivo such that it can be cleaved by RNase P to generate the 5' end of the mature 10Sa RNA. The purified 10Sa RNA can be charged with alanine in vitro. Disruption of the gene encoding 10Sa RNA (ssrA) caused a reduction in the rate of cell growth, which was especially apparent at 45 degrees C, and a reduction in motility on semisolid agar. These phenotypic characteristics of the deletion strain (delta ssrA) allowed us to investigate the effects of some mutations in 10Sa RNA in vivo, although the exact function of 10Sa RNA still remains unclear. When the G.U pair (G3.U357) in 10Sa RNA, which may be equivalent to the determinant G.U pair of alanine tRNA, was changed to a G.A or G.C pair, the ability to complement the phenotypic mutations of the delta ssrA strain was lost. Furthermore, this inability to complement the mutant phenotypes that was caused by the substitution of the determinant bases by a G.A pair could be overcome by the introduction of a gene encoding alanyl-tRNA synthetase (alaS) on a multicopy plasmid. The evidence suggests that the proposed structural features of 10Sa RNA are indeed manifested in vivo.

Base Sequence↗

PubMed1994

Effects of inhaled nitric oxide in rats with chemically induced pulmonary hypertension.

To determine the model animal with pulmonary hypertension in which nitric oxide (NO) inhalation reduces pulmonary arterial pressure (PAP), we examined the inhalation of 20-100 ppm NO gas on normal rats and rats with monocrotaline induced pulmonary hypertension. In the control group, mean PAP showed no change after spontaneous breathing of NO at the concentration of 20 to 100 ppm for 5 min. On the contrary, in both the severe (mean PAP > 40 mmHg) and moderate (mean PAP < 40 mmHg) pulmonary hypertensive groups, NO inhalation produced a prompt reduction of the mean PAP which had been elevated by monocrotaline. 20 ppm NO inhalation reduced mean PAP from 64.4 +/- 3.7 mmHg to 56.2 +/- 4.4 mmHg (mean +/- SEM, P < 0.01) in the severe pulmonary hypertensive group, from 31.0 +/- 2.0 mmHg to 24.2 +/- 0.9 mmHg in the moderate pulmonary hypertensive group (mean +/- SEM, P < 0.05). The onset of the reduction of mean PAP occurred within 30 sec after the start of NO inhalation and maximum reduction occurred within 4 min. 20 ppm NO inhalation significantly reduced mean PAP, and mean PAP was reduced dose-dependently at the concentration of 20 to 60 ppm and reaction to NO was almost constant at the concentrations of over 60 ppm.

Administration, Inhalation↗

PubMed1993

A simplified method for generating step-wise deletions using PCR.

A simple and general method is described for the generation of ordered deletions for DNA sequencing. Nicked plasmids, the substrates for step-wise digestion by exonuclease III, are obtained after the self-ligation of PCR products with phosphorylated and non-phosphorylated primers and plasmid DNAs as template. The method is suitable for use with any plasmid vector and for generation of deletion clones with deletions in both possible directions.

Base Sequence↗

PubMed1992

Procedure for evaluating changes in respiratory symptoms of experimentally asthma-induced guinea pigs by a personal computer.

An automated system was developed for evaluating changes in respiratory symptoms in guinea pigs over a long period with a personal computer. The data on breathing curves obtained with a body plethysmograph were analyzed to determine respiratory rate, expiration/inspiration ratio, ventilation ratio, and other parameters. With this system, respiratory changes in guinea pigs, such as increase or decrease of respiratory rate, expiration/inspiration ratio, and ventilation ratio, and death of animals could be easily observed. Investigation of delayed respiratory response to Candida albicans in sensitized guinea pigs and of the effects of SO2 or NO2 exposures on its response was carried out using this system. Respiratory changes in delayed respiratory response were mostly increased respiration rate and succeeding expiratory prolongation being noted just before death. In the influences of SO2 or NO2 exposure on delayed respiratory response, increase of respiratory rate in NO2 and expiratory and inspiratory prolongation in SO2 were found. This system should prove useful for evaluating changes in respiratory symptoms due to toxic agents, medicines, and air pollutants in small animals.

Animals↗

PubMed1991

Effects of exposure to sulfate aerosols and antigen on breathing curve patterns of guinea pigs.

We investigated the effects of ammonium sulfate aerosols on asthmatic dyspnea (immediate type) induced by repeated inhalation of a mixture of bovine serum and egg albumin and on the nonspecific responsiveness of the airway tract to acetylcholine. Guinea pigs were exposed to sulfate aerosol in concentrations of 0.2, 0.4, and 2.0 mg/m3 and to 0.2 mg/m3 sulfate aerosol combined with 0.1 ppm of SO2. The exposure time was 2 h/d, 5 d/wk, 38 times in all. The animals were successively exposed to aerosol (for 2 h) and, after 30 min, to the spraying of albumin solution 3 times per week, 7 or 9 times in all. Breathing curves were continuously recorded by a body plethysmograph system during the sensitization periods. The experiments showed that the degree of asthmatic dyspnea in guinea pigs was increased by the exposure to aerosol, and that there is a quantitative relation between the severity of the dyspnea and extent of the exposure. Exposure in the combination with SO2 showed no effect at the concentration studied. Following the exposure experiment, each group of animals was exposed to the spraying of acetylcholine. The sensitivity to acetylcholine increased at aerosol concentrations of 0.4 and 2.0 mg/m3.

Acetylcholine↗

PubMed1988

Biochemical characterization of scleroderma-inducing glycosaminoglycan.

The scleroderma-inducing N-sulfated glycosaminoglycan previously isolated by us from the urine of patients with systemic scleroderma was further purified: it was biochemically characterized by low O-sulfation and relative high N-sulfation. Consistent with this finding, desulfated and N-resulfated heparin, which had a similar composition to the urine-derived scleroderma-inducing glycosaminoglycan, induced a significant degree of sclerotic fibrosis in the skin of mice which had received intraperitoneal injections of it, whereas N-desulfated heparin with contrasting sulfation to it failed to cause any significant change in the skin.

Animals↗

PubMed1987

Significant increase of urinary low-sulfated heparan-sulfate-related protein in patients with severe systemic scleroderma.

Radioimmunoassay with an antibody produced against urinary low-sulfated heparan-sulfate-related protein was devised and used to screen the heparan sulfate level in the urine of patients with systemic scleroderma. Patients with diffuse scleroderma, and patients also showing polymyositis/dermatomyositis had elevated values, whereas the value in patients with acrosclerotic scleroderma did not differ from that of the control population. In addition, an increase in this protein was associated with the positivity of anti-Scl-70 antibody. These findings suggest an important role for low-sulfated heparan sulfate in the pathobiology of severe systemic scleroderma.

Adult↗