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Biomedical subjects

S Nishima

Publications and source records attributed to S Nishima.

At least 19 recordsLinked to original sources

Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood atopic asthma.

BACKGROUND: IFN-gamma and related molecules play important roles in the differentiation and function of TH2 cells. OBJECTIVE: We sought to determine whether IFNG and related genes contribute to any susceptibility to atopic asthma, a representative TH2-dominant disorder. METHODS: We investigated the association of IFNG (CA repeat polymorphism within the first intron), IRF1 (GT repeat polymorphism within the intron 7), IFNGR1 (Val 14 Met), and IFNGR2 (Gln 64 Arg) gene polymorphisms with atopic asthma in the Japanese child population. RESULTS: A significant association (P =.0018) was observed between IFNG gene polymorphism and atopic asthma. The tendency was more prominent in patients with age of onset of 3 years or younger (P =.0004) or patients with a family history of allergic diseases (P =.0038). Furthermore, there was a significant association between IRF1 gene whole-allele distribution and atopic asthma (P =.044). The tendency was more prominent in patients with onset at 3 years of age or less (P =.0058). On the other hand, IFNGR1 and IFNGR2 gene polymorphisms showed no association with atopic asthma. CONCLUSION: These results suggested that among IFNG and related genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in Japanese children.

Adolescent↗

Acute interstitial pneumonia induced by ONO-1078 (pranlukast), a leukotriene receptor antagonist.

A 62-year-old woman treated with pranlukast for 2 months developed interstitial pneumonitis with a high fever. A lymphocyte stimulation test was reactive to pranlukast. Her clinical symptoms improved with discontinuation of pranlukast and administration of systemic corticosteroid. To our knowledge, this is the first reported case of drug-induced lung disease involving a leukotriene. The steps that can be taken to promptly reach a diagnosis and to successfully treat this life-threatening condition are described.

Acute Disease↗

[Long-term study of airborne allergic pollen count, C. Japonica and cupressaceae in Japan].

We have investigated the distribution of airborne pollen at the different eleven points in Japan from 1987 to 1998 using gravity sampler. To clarify the characteristics causative pollen for Japanese cedar pollinosis, we examined annual change of pollen counts, dispersing period and geographical difference of C. japonica and Cupressaceae pollen. C. japonica pollen occupied much more in Central Japan and Cupressaceae in the west of Japan than the other area. In Hamamatsu City, both of pollen counts were most of all and we found a tendency that the more pollen counts the longer dispersing period. As they reported that at the starting day of pollen in this method some patients had already suffered from allergic symptoms, we considered pollen grains were dispersing in spite of being continuously captured. In these twelve years we found that patients with Japanese pollinosis are exposured by causative agents during about 100 days every spring. But we could not observe the trend of increasing pollen counts and earlier starting day because of global warming. Further more we found that the pollen counts of C. japonica in autumn was increasing since 1994. As one of the factors of increasing patients with pollinosis, we thought that total exposure period of causative pollen every year were longer than that of 1980s.

Air Pollutants↗

[The impact of obesity on oxygen desaturation in patients with sleep apnea/hypopnea syndrome].

We performed a cross-sectional investigation on the impact of obesity on clinical manifestations in patients with obstructive sleep apnea/hypopnea syndrome (SAHS). The subjects were 87 patients who underwent overnight polysomnography with an apnea/hypopnea index (AHI) of 15/h or more. We divided these patients into non-obese (N) and obese (O) groups based on the median value of the body mass index (BMI), 27 kg/m2. Subjective symptoms, sleep quality and AHI were similar in both groups, but every parameter related to oxygen desaturation was worse in group O than in group N. There was no difference in the mean duration of apnea events between the two groups. The rate of fall in oxygen saturation during apnea events was highly correlated to the BMI (r = 0.72; p < 0.00001). Accordingly, we concluded that profound desaturation in group O is due to a rapid fall in oxygen saturation during apnea events compared with group N. Anthropometric measurements revealed that the rate of fall in oxygen saturation was more related to abdominal circumference (AC) than the neck circumference (NC), which is contrasted with the finding that AHI was more related to NC than AC. This fact suggests that abdominal obesity may deteriorate oxygenation during apnea events and may therefore aggravate the risk of cardiovascular disease in patients with SAHS.

Adult↗

Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes guinea pig tracheal smooth muscle by producing epithelium-dependent relaxing factors.

A non-phorbol ester-type tumor promoter, thapsigargin has been reported to deplete Ca(2+) stores in endothelial cells by inhibiting Ca(2+)-ATPase, which in turn increases intracellular Ca(2+) by mobilization of extracellular Ca(2+), leading to activation of constitutive nitric oxide synthase (cNOS) and resultant generation of nitric oxide (NO). In the present study, to evaluate the role of Ca(2+) in the release of epithelium-dependent relaxing factor (EpDRF), we determined the effect of thapsigargin (10(-6) M) on the contraction evoked by exogenous Ca(2+) or acetylcholine (10(-5) M) in epithelium-denuded or epithelium-intact smooth muscle from guinea pig trachea. The following results were obtained: (1) In epithelium-denuded smooth muscle, the contraction evoked by exogenous Ca(2+) in Ca(2+)-free solution or by acetylcholine (10(-5) M) in Ca(2+)-containing solution did not change within 20 min after thapsigargin application, but the contraction evoked by exogenous Ca(2+) increased markedly after 120 min, indicating that thapsigargin had no effect on smooth muscle itself within 20 min of application. The following experiments were performed within 20 min of thapsigargin application. (2) In epithelium-intact smooth muscle, thapsigargin significantly suppressed the contraction evoked by acetylcholine, suggesting that thapsigargin stimulate the epithelium to produce EpDRF. N(G)-nitro-L-arginine methylester (L-NAME) partly, but significantly, attenuated this inhibitory effect of thapsigargin. (3) In epithelium-denuded smooth muscle, atropine (10(-6) M) and L-NAME (10(-5) M) did not change the contraction evoked by exogenous Ca(2+) after application of thapsigargin, suggesting that thapsigargin did not stimulate acetylcholine and NO release from nerve terminals. These results suggest that thapsigargin (10(-6) M) may stimulate EpDRF, including NO and other factor(s) by Ca(2+)-dependent mechanisms.

Acetylcholine↗

Neutrophil elastase inhibitor, ONO-5046 suppresses ozone-induced airway mucus hypersecretion in guinea pigs.

To investigate the role of neutrophil elastase in ozone-induced airway hypersecretion, we measured goblet cell secretion by using a semiquantitative morphometric technique in guinea pigs. The magnitude of mucus discharge was estimated from the mucus score, which is inversely related to the degree of mucus discharge in histological sections of trachea stained for mucus glycoprotein with periodic acid Schiff/Alcian blue. Mucus hypersecretion of goblet cells was induced by ozone exposure and persisted for up to 5 h after exposure. Pretreatment with N-[2-¿4-(2,2-dimethyl-propionyloxy) phenyl-sulfonylamino¿ benzoyl] aminoacetic acid (ONO-5046), a specific neutrophil elastase inhibitor (200 mg/kg, intraperitoneally), significantly inhibited goblet cell hypersecretion both just after and 5 h after ozone-exposure, but the latter inhibition was not complete. In bronchoalveolar lavage fluid, ozone exposure significantly increased the number of neutrophils just after and 5 h after exposure, while ONO-5046 significantly inhibited the increase in neutrophils only 5 h after ozone-exposure. These results indicate that neutrophil elastase may play an important role in the ozone-induced tracheal goblet cell hypersecretion and influx of neutrophils.

Animals↗

Novel polymorphism in the coding region of the IL-13 receptor alpha' gene: association study with atopic asthma in the Japanese population.

Interleukin (IL)-4 and IL-13 play key roles in the development of atopic asthma. The IL-13 receptor (R) alpha' chain is a component of both IL-4R and IL-13R complexes. By screening the whole coding region of the IL-13Ralpha' gene for polymorphisms, we identified a new polymorphism at nucleotide position 1050 from the ATG start codon. The allelic frequency of the C/T polymorphism in the Japanese population was found to be 0.97:0.03. Because of the low frequency of the T allele, the association study failed to indicate any significant association between this polymorphism and atopic asthma in the Japanese population. Further studies are required in other racial groups with higher frequencies of this polymorphism to elucidate the association.

Alleles↗

Childhood atopic asthma: positive association with a polymorphism of IL-4 receptor alpha gene but not with that of IL-4 promoter or Fc epsilon receptor I beta gene.

We examined the relative contributions of three representative candidate genes for atopy (Fc epsilon receptor I beta, IL-4, and IL-4 receptor alpha) to the development of atopic asthma. Four polymorphisms of the three candidate genes including Ile50Val and Gln551Arg of IL-4 receptor alpha, -590C/T of IL-4 promoter and Glu237Gly of Fc epsilon receptor I beta were studied in 100 patients with atopic asthma and 100 nonatopic controls in the northern Kyushu area in Japan. Among the four polymorphisms of the three candidate genes, the Ile50 allele of the IL-4 receptor alpha chain gene demonstrated an association with atopic asthma subjects (p = 0.044), especially in patients with onset at 2 years of age or earlier (p = 0.034) and in patients with moderate to severe atopic asthma (p = 0. 031). Gln551Arg of IL-4 receptor alpha, -590C/T of IL-4 promoter and Glu237Gly of Fc epsilon receptor I beta showed no association with atopic asthma. A slight linkage disequilibrium between Ile50Val and Gln551Arg polymorphisms of the IL-4 receptor alpha chain gene was observed in both patients and nonatopic controls. The identification of additional atopy genes in areas with a certain genetic background is essential for genetic diagnosis and to establish new therapeutic modalities for atopic asthma.

Adolescent↗

Lack of association between CD28/CTLA-4 gene polymorphisms and atopic asthma in the Japanese population.

Atopic asthma occurs in genetically susceptible individuals in the presence of environmental factors. Recently, the costimulation signal from CD80-CD86 to CD28/CTLA-4 has been suggested to play an important role in the development of atopic asthma. In the present study, we analyzed three polymorphic regions within the CTLA-4 gene, an A/G substitution in exon 1 position 49, a C/T base exchange in the promoter position -318 and an (AT)n repeat polymorphism in the 3'-untranslated region of exon 4, and a CD28 gene polymorphism with a T/C substitution in intron 3 position +17 in 120 patients with atopic asthma and 200 normal controls. The polymorphism frequencies of CTLA-4/CD28 genes in patients did not differ from those in normal controls. Thus, the present study was unable to reveal any association between CTLA-4/CD28 gene polymorphisms and atopic asthma in the Japanese population.

Abatacept↗

[The relationships of mononuclear leukocyte beta-adrenergic receptors to aerobic capacity and exercise-induced asthma in asthmatic children].

beta-adrenaline receptors exist on peripheral mononuclear leukocytes as well as in lung tissue. We assessed the relationships of plasma catecholamine release by exercise to aerobic capacity and to exercise-induced asthma (EIA) in asthmatic children (Study 1). We then measured mononuclear leukocyte beta-adrenergic receptor densities at rest and assessed the relationships of the number of receptors to aerobic capacity, EIA, and bronchial responsiveness to acetylcholine (Study 2). Study 1: Eleven children (9 males, 2 females; 11-16 years old) with bronchial asthma participated in this study. The subjects underwent an incremental aerobic exercise test on a cycle ergometer to determine their aerobic capacity at the lactic threshold (LT) and VO2max. Each subject underwent an EIA test of which the intensity was 175% of LT, and plasma catecholamine concentrations were measured before and after exercise. A significant negative relationship was found between the degree of EIA and % change of plasma adrenaline concentrations to rest level (p < 0.05), and a significant positive relationship was found between VO2 max/wt and % change of plasma adrenaline concentrations (p < 0.05). Study 2: Twelve asthmatic children (10 males, 2 females; 11-16 years old) participated in this study. Aerobic capacity, and degree of EIA were also measured in each subject by the same method as that used in Study. 1. The number of mononuclear leukocyte beta-adrenergic receptors at rest was determined by (-) [125I]-iodocyanopindolol binding in each subject. A significant negative relationship was found between the number of adrenergic receptors and Max. % fall in FEV1.0 (p < 0.01), and a significant positive relationship was found between the number of adrenergic receptors and VO2max/kg (p < 0.001). These results suggested that a reduced adrenaline production and a reduced number of beta-receptors contributed to the pathogenesis of EIA.

Adolescent↗

[A simple personal computer-based system for lung sound analysis].

Although lung sounds provide important information about the respiratory system, the analysis of lung sounds has not been widely used in clinical practice because of the complicated procedure involved. However, personal computer technology has made impressive strides in recent years. Today, practically all personal computer models on the market are equipped with the capacity for audio signal input and output. We developed a new computer system for lung sounds acquisition and analysis. The system hardware comprises only a personal computer and a microphone, and the software was developed for a widely used operating system (Windows 95). Our system can record, save, and replay lung sounds and analyze their time and frequency domains. To verify the accuracy of sound acquisition, we examined the frequency characteristics of the system as installed and utilized on 4 different machines. The characteristics were essentially flat throughout the 200-2,000 Hz spectrum within which almost all lung sounds were contained. We feel our system can serve as a simple and useful tool for lung sound analysis.

Humans↗

[Subcutaneous sarcoidosis of the extremities].

A 65-year-old man was referred to our hospital due to abnormal chest roentgenograms showing bilateral hilar enlargement with diffuse micronodular opacities. He presented with uveitis and elevated serum ACE and tested negative for tuberculin response. Transbronchial lung biopsies as well as bronchoalveolar lavage were performed and yielded a diagnosis of sarcoidosis. Several months later, the patient showed multiple subcutaneous nodules around the knee joints and elbow joints with exacerbation of intrapulmonary lesions. A skin biopsy revealed multiple foci of typical non-caseating epithelioid cell granulomata. These pulmonary and subcutaneous lesions rapidly resolved in response to the systemic administration of corticosteroids. Subcutaneous sarcoidosis may be a subacute variant of sarcoidosis associated with systemic involvement.

Aged↗

Novel polymorphism in the 5'-untranslated region of the interleukin-4 gene.

We found a novel polymorphism C/T change at position -34 counting from the first ATG codon, of the interleukin-4 (IL-4) gene, located between the TATA box and the first ATG on exon 1. The allelic frequency of this C/T polymorphism in 64 independent Japanese samples was 0.37:0.63. In addition, PCR-restriction fragment length polymorphism analysis revealed that the -34T/T polymorphism was always associated with -590T/T, a known polymorphism that increases IL-4 transcriptional activity.

5' Untranslated Regions↗

Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma.

BACKGROUND: A study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma. METHODS: Eight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child's lactate threshold (LT), measured using a swimming ergometer. Another group of eight asthmatic children served as control subjects. Aerobic capacity and the degree of EIB were assessed by both cycle ergometer and swimming ergometer before and after swimming training. RESULTS: The mean (SD) aerobic capacity at LT increased by 0.26 (0.11) kp after training when assessed with the swimming ergometer and by 10.6 (4.5) W when assessed with the cycle ergometer, and these changes were significantly different from the control group. The mean (SD) maximum % fall in forced expiratory volume in one second (FEV1) to an exercise challenge (cycle ergometer) set at 175% of LT decreased from 38.7 (15.4)% before training to 17.9 (17.6)% after training, but with no significant difference from the control group. There was, however, no difference in histamine responsiveness when compared before and after the training period. CONCLUSION: A six week swimming training programme has a beneficial effect on aerobic capacity but not on histamine responsiveness in children with asthma.

Asthma↗

[Change in prevalence of allergic diseases in primary school children in Fukuoka City for the last fifteen years].

We have been investigating the yearly change of prevalence rate of childhood allergic diseases using same method and in same region in five primary schools in Fukuoka City for the last fifteen years. From 1981 to 1995, revised ATS-DLD questionnaire had been administered yearly to the first graders of primary school children (6-7 yrs). The total number of subjects for fifteen years were 8000. The average number of children in each year was 533. 1. The cumulative prevalence of bronchial asthma statistically increased from 5.7% (average of 1981 to 1983) to 7.7% (1993 to 1995). It was 1.7 times higher on boys. 2. The cumulative prevalence of atopic dermatitis did not change yearly and its average was 36.3%. The boys/girls ratio was 1.2. Remission rate of atopic dermatitis statistically increased from 14.3% (average of 1987 and 1988) to 19.6% (1994 and 1995). 3. The cumulative prevalence of allergic rhinitis did not change yearly and its average was 17.6%. It was 1.5 times higher on boys. 4. The cumulative prevalence of allergic conjunctivitis statistically increased from 8.4% (average of 1987 and 1988) to 11.1% (1994 and 1995).

Child↗

[Evaluation of sleep fragmentation by EEG spectrography in patients with obstructive sleep apnea syndrome].

Sleep fragmentation is considered to have a central role in the pathophysiology of sleep-disordered breathing. However, the evaluation of sleep fragmentation can be very troublesome work. We sought to evaluate sleep fragmentation in 10 patients with obstructive sleep apnea syndrome by utilizing fast-fourier transforms to render their sleep encephalograms as spectrograms (horizontal axis: time, vertical axis: frequency, color: power). Detailed 5-minute spectrograms revealed relatively uniform patterns of change in EEG spectra during and after apnea episodes. In non-REM sleep, delta activity during apnea was followed by alpha and beta activity during resumed breathing. In REM sleep, flat and low-power spectral patterns during apnea were followed by relatively weak alpha and beta activity during resumed breathing. In compressed, 1-hour views of the spectrograms, repeated apnea events appeared as vertical striped patterns of spectral change. These patterns were thought to be representative of sleep fragmentation. The spectrographic display of EEGs may be a very simple and easy method for the evaluation of sleep-fragmentation in sleep disordered breathing.

Adult↗