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Y Ohki

Publications and source records attributed to Y Ohki.

At least 19 recordsLinked to original sources
PubMed2001

A deteriorated triple-helical scaffold accelerates formation of the Tetrahymena ribozyme active structure.

The Tetrahymena group I ribozyme requires a hierarchical folding process to form its correct three-dimensional structure. Ribozyme activity depends on the catalytic core consisting of two domains, P4-P6 and P3-P7, connected by a triple-helical scaffold. The folding proceeds in the following order: (i) fast folding of the P4-P6 domain, (ii) slow folding of the P3-P7 domain, and (iii) structure rearrangement to form the active ribozyme structure. The third step is believed to directly determine the conformation of the active catalytic domain, but as yet the precise mechanisms remain to be elucidated. To investigate the folding kinetics of this step, we analyzed mutant ribozymes having base substitution(s) in the triple-helical scaffold and found that disruption of the scaffold at A105G results in modest slowing of the P3-P7 folding (1.9-fold) and acceleration of step (iii) by 5.9-fold. These results suggest that disruption or destabilization of the scaffold is a normal component in the formation process of the active structure of the wild type ribozyme.

Animals↗
PubMed2001

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Journal Article↗
PubMed2001

Self-splicing of the Tetrahymena group I ribozyme without conserved base-triples.

BACKGROUND: Group I introns share a conserved core region consisting of two domains, P8-P3-P7 and P4-P6, joined by four base-triples. We showed previously that the T4 td intron can perform phosphoester transfer reactions at two splice sites in the absence of both P4-P6 and the conserved base-triples, whereas it is barely able to perform the intact splicing reaction due to the difficulty of conducting the sequential reactions. RESULTS: Based on previous findings, we constructed a bimolecular ribozyme lacking a large portion of P4-P6 and the base-triples from the Tetrahymena intron, on the assumption that the long-range interactions of the peripheral regions in the two RNAs can compensate for the deteriorated core. The bimolecular ribozyme performed the intact splicing reaction. CONCLUSION: The present analysis indicates that the base-triples are nonessential, but that L4 and the distal part of P4 in P4-P6 are important for conducting the splicing reaction. The reconstituted self-splicing ribozyme provides an amenable system for analysing the role(s) of elements in the core region in the self-splicing reaction mechanism.

Animals↗
PubMed2001

Elevated type IV collagen in bronchoalveolar lavage fluid from infants with bronchopulmonary dysplasia.

We measured the levels of type IV collagen and lipid peroxides in bronchoalveolar lavage fluid (BALF) from infants with respiratory distress syndrome (RDS) to determine the relationship to the development of bronchopulmonary dysplasia (BPD). We analyzed their levels between two groups, RDS infants who developed BPD (n = 8, BPD group) and those who did not (n = 11, RDS group). The levels of the type IV collagen in the BPD group were significantly higher than those in the RDS group at 3 and 7 days of age (p = 0.0024). In the BPD group, persistently increased levels of the type IV collagen were observed during the period up to 14 days of age. There was a positive relationship between the type IV collagen levels and polymorphonuclear leukocyte counts, and thiobarbituric acid-reactive substance levels in BALF. These results suggest that the increased type IV collagen levels in BALF of BPD infants may reflect pulmonary basement membrane damage and the involvement of oxygen metabolites in its process.

Birth Weight↗
PubMed2001

[The relation between the severity of bronchial asthma and the treatment points in children].

The treatment points and score for definition of the asthma severity were initially introduced in the guideline for pediatric asthma treatment and management on 1998. We studied the relationship between the severity of clinical symptoms for children with bronchial asthma and the treatment points from July 1998 to November 1999 in our hospital. One hundred twenty five patients (one to 15 years of age, 77 boys and 48 girls) were retrospectively investigated. The treatment points and scores were associated with the clinical symptom score. However, there was no relationship in some patients. In order to define the severity of bronchial asthma, we should investigate not only the severity in terms of the clinical symptoms; the number and degree of asthma attacks, but also the treatment points and score. Furthermore, we should pay attention to the seasonal variation of the treatment points.

Adolescent↗
PubMed2000

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Journal Article↗
PubMed2000

Ultrasonographic detection of very thin percutaneous central venous catheter in neonates.

To assess the ability of ultrasonography to detect the tip of a very thin (0.4 mm outer diameter) percutaneous central venous catheter (PCVC) in neonates, the PCVC tip location was assessed by ultrasonography (US) and compared to the location estimated by standard radiography for 57 PCVCs in 44 neonates. Of 57 occasions, the examiner could not find the PCVC tip in three cases (5%). In the remaining 54 instances, in 87% of cases, the PCVC tip position was consistent with the location implied by skeletal landmarks on standard radiographs. On 24 occasions we also assessed catheter tip dislodgement according to flexion and extension of the infant's arm. US could detect 78% of cases of catheter tip dislodgement. The PCVC tip was sometimes visualized as a dot and parallel lines as well as mere parallel lines. In a large population of cases, US is a reliable method for detection of a thin PCVC tip. US provides precise information about the PCVC tip position in relation to vascular structure and contributes to safer positioning of the PCVC than traditional radiography alone.

Age Factors↗
PubMed1999

Sensorimotor interactions between pairs of fingers in bimanual and unimanual manipulative tasks.

The tuning of fingertip forces to the physical properties of objects during manipulation may be controlled partly by digit-specific mechanisms using local afferent information and partly by controllers that support interdigital coordination and use sensory information from more than one digit. In the present study we addressed digital interactions when humans used the tips of two fingers to restrain a pair of horizontally oriented plates from moving when subjected to tangential force loads in the distal direction. Subjects used the right and left index fingers in a bimanual grasp, and the right index and middle fingers in an unimanual grasp. The plates were loaded at unpredictable times by identical force profiles consisting of a force increase of up to a 3-N force plateau. The plates were concurrently loaded in 85% of the trials and each plate was loaded separately in 7% of the trials. For each plate, we measured its movement and the normal and tangential forces applied by the finger to restrain it. When a finger was loaded, the subject automatically responded by a normal force increase to a level that remained fairly constant during the subsequent load plateau. The initial part of this finger grasp response was affected by simultaneous loading of its partner finger; the magnitude of the response was boosted with a bimanual grasp, whereas the onset latency tended to be shorter with a unimanual grasp. Responses also occurred at a non-loaded finger during both bimanual and unimanual grasps, but these responses were weaker than those evoked when the same finger was loaded. In the bimanual grasp, they were largely characterized by a brief force pulse whose onset was delayed by some 15 ms compared with the response onset of the loaded finger, i.e., there was no sustained response. In the unimanual grasp, the onset of the response coincided in time with that of the accompanying (loaded) finger, and the dynamic response was stronger and prolonged, with more than one force rate peak. There was also a significant static response present. We conclude that during unimanual as well as bimanual reactive restrain tasks there are interactions between digits engaged in terms of neural control that facilitate the response of a digit when an accompanying digit is simultaneously loaded. However, digit-specific afferent inputs are necessary for eliciting the full-size reactive grasp responses required to successfully restrain the manipulandum.

Adult↗
PubMed1999

Transtubular potassium concentration gradient in preterm neonates.

To determine the postnatal changes in mineralocorticoid action on the cortical distal nephron in preterm neonates, we evaluated the transtubular potassium gradient (TTKG) and its relationship to other renal and non-renal parameters in 16 preterm neonates during the first 5 weeks of life. Preterm neonates were divided into two groups according to their gestational age: the first group (group A, n=9) had a gestational age less than 30 weeks and the second group (group B, n=7) had a gestational age over 30 weeks. TTKG in both groups increased significantly with postnatal age, and TTKG in group A was significantly lower than that in group B (P=0.0003; two-way repeated analysis of variance). TTKG in group A was significantly lower during the 2 weeks of postnatal life than that in full-term neonates [TTKG during 1st week (mean+/-SD) 3.73+/-1.32, P<0.00001; during 2nd week 7.77+/-3.60, P=0.0096 versus full-term neonates (n=19); 11.56+/-3.23]. TTKG in group B was significantly lower only during the 1st week of life (6.55+/-2.71, P=0.0013) compared with full-term neonates. Plasma aldosterone concentration did not correlate with TTKG value. Stepwise regression analysis showed that postnatal age, cortical lumen sodium concentration (CLNa), and clinical condition requiring the use of mechanical ventilation were independent variables that correlated significantly with TTKG. We postulate that the low TTKG level in preterm neonates might reflect the prematurity of renal function (early postnatal age, CLNa) and the condition(s), relating to immaturity, such as the use of mechanical ventilation.

Age Factors↗
PubMed1999

Effect of ultrasonically nebulized distilled water on airway epithelial cell swelling in guinea pigs.

To investigate the pathogenesis of ultrasonically nebulized distilled water-induced airway narrowing, we studied the role of airway epithelial cells during a distilled water-inhalation challenge in an animal model of airway inflammation. Guinea pigs were divided into four groups: 1) a sham/saline (S/S) group: sham ozone followed by saline inhalation; 2) a sham/water (S/W) group: sham ozone followed by water inhalation; 3) an ozone/saline (O/S) group: ozone followed by saline inhalation; and 4) an ozone/water (O/W) group: ozone followed by water inhalation. After exposure to either 3.0 parts/million ozone or air at the same flow rate for 2 h, guinea pigs were anesthetized and tracheostomized, and then lung resistance (RL) was measured. For morphometric assessment, tissues were fixed with formaldehyde, stained with hematoxylin and eosin, and cut into transverse sections. Airway dimensions were either measured directly or calculated from the internal perimeter, the external perimeter, and airway wall area. There were no statistical differences in the values of RL before distilled water inhalation between the sham groups and the ozone groups. RL increased significantly after 10 min of distilled water inhalation in both the S/W group and the O/W group. In the S/W group, epithelial cells were swollen, and intercellular spaces were wider, resulting in significant increase in epithelial wall thickness, but there was no significant infiltration by inflammatory cells. In the O/S group, the epithelium showed infiltration by inflammatory cells without change in cell volume. In the O/W group, the epithelium showed both infiltration and a greater increase in epithelial wall thickness compared with the S/W group. These results suggest that airway epithelial cell swelling, induced by inhaled distilled water, increases with RL in guinea pigs and that this reaction may be accelerated by airway inflammation.

Administration, Inhalation↗
PubMed1999

Disynaptic pyramidal excitation in forelimb motoneurons mediated via C(3)-C(4) propriospinal neurons in the Macaca fuscata.

In contrast to findings in the cat, it recently has been shown that disynaptic pyramidal EPSPs only rarely are observed in forelimb motoneurons of the macaque monkey in the intact spinal cord or after a corticospinal transection in C(5). This finding has been taken to indicate that the disynaptic pyramidal excitatory pathway via C(3)-C(4) propriospinal neurons (PNs) is weakened through phylogeny when the monosynaptic cortico-motoneuronal connection has been strengthened. We reinvestigate this issue with special focus on the possibility that the inhibitory control of the C(3)-C(4) PNs may be stronger in the macaque monkey than in the cat. The effect in forelimb motoneurons of electrical stimulation in the contralateral pyramid was investigated in anesthetized macaque monkeys (Macaca fuscata). We confirmed the low frequency of disynaptic pyramidal EPSPs in forelimb motoneurons. However, after intravenous injection of strychnine, disynaptic EPSPs could be evoked in 39 of 41 forelimb motoneurons recorded after lesion of the corticospinal fibers in C5. After a corresponding lesion in C(2), disynaptic pyramidal EPSPs were observed in 2 of 25 motoneurons. In contrast to previous reports, we conclude that C(3)-C(4) PNs can mediate disynaptic pyramidal excitation in high frequency of occurrence to forelimb motoneurons in the C(6)-C(8) segments and that this transmission is under a stronger inhibitory control than in the cat. Thus, the hypothesis that the disynaptic excitatory cortico-motoneuronal pathway via the C(3)-C(4) PNs is weakened in parallel with the strengthened monosynaptic connection through phylogeny is not supported by the present findings.

Anesthesia↗
PubMed1999

Bronchial reactivity to inhaled methacholine in infants with asthma and age-matched controls.

To evaluate bronchial hyperresponsiveness (BHR) in infants with asthma and the influence of aging on BHR during the infantile period, bronchial reactivity to inhaled methacholine (BRm) in infants was monitored using the transcutaneous oxygen pressure (tcPO2) method. One hundred thirty-seven infants with asthma (from 1 to 5 years, mean 3.4 years) and 97 age-matched children without chronic respiratory diseases (from 6 months to 5 years, mean 2.1 years) were enrolled in this study. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO2 from the baseline was reached. The cumulative dose of methacholine at the inflection point of tcPO2 (Dmin-PO2) was considered to represent the reactivity of tcPO2 to inhaled methacholine. Dmin-PO2 values in the asthma groups were lower than those in the control groups in each year-group from 1 to 5. There was no statistical difference in Dmin-PO2 among the 1-4-year-old asthma groups, but Dmin-PO2 in the 5-year-old asthma group was significantly lower than Dmin-PO2 in the 1-4-year-old asthma groups. The same age-related change in Dmin-PO2 was also seen in the control groups. There was no difference in age-related Dmin-PO2 change between the female group and the male group. We concluded that BRm in asthmatic children increases during the infantile period, and that the age-related changes in BRm, observed in both asthmatic and control infants, may have an effect on the clinical symptoms of asthma during childhood.

Age Factors↗
PubMed1998

Transcutaneous oxygen tension measurements during methacholine challenge of prematurity in infants with chronic lung disease.

Chronic lung disease (CLD) of prematurity may be caused by a number of insults during mechanical ventilation, including barotrauma and hyperoxia. To evaluate bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we measured changes in transcutaneous oxygen tensions (tcPO2) during methacholine inhalation challenge. Twelve infants with CLD and 22 age-matched children without respiratory diseases were enrolled in this study (ages--5 to 36 months; mean age--16.2 months). Serial doses of methacholine were doubled until a 10% decrease in tcPO2 from baseline was reached. The cumulative dose of methacholine inhaled by the time tcPO2 had been reached (Dmin-PO2) was considered to represent the dose at which reactivity to methacholine (RO2meth) had occurred. In the CLD group, Dmin-PO2 (3.50 +/- 0.1 log x milli-units) was significantly lower than in the preterm control infant group (4.31 +/- 0.2 log x milli-units) and the term infant group (4.21 +/- 0.1 log x milli-units) (P = 0.004, P < 0.001). Dmin-PO2 in the preterm control infant group was not significantly different than in the term infant group (P > 0.5). These results suggest that infants who require additional therapeutic oxygen and mechanical ventilation during the early months of life are at risk of developing early-onset, long-lasting respiratory disease that is related to an acquired BHR.

Bronchial Hyperreactivity↗
PubMed1997

Percutaneous central venous catheterization via the great saphenous vein in neonates.

In 44 neonates (mean birthweight 1207 g and mean gestational age 30.0 weeks), very small central venous catheters were percutaneously inserted via the great saphenous vein on 46 occasions. Catheter-related complications such as catheter blockages in 17 (37%), edema in a unilateral leg in three (6%), and mechanical disruption in two (4%) were noted. Although two of the neonates were found to have bacteremia and five neonates died, none were catheter related. The optimal length of catheter insertion (Y) from the great saphenous vein at the level of the medial maleollus to the inferior vena cava at T9 and L3 was calculated by regression equations utilizing total body length (X). Radiographs taken with extended and flexed leg postures revealed that the catheter tips were retracted with extension of the lower extremities and the degree of displacement ranged from 1 to 4 (mean 2.7) vertebral levels. Because this movement might cause migration into veins that connect to the inferior vena cava, the catheter tip should be located between T9 and L3, except at the renal vein junction. Percutaneous central venous catheterization via the great saphenous vein is safe and useful. Regression equations provided for rapid estimation of the optimal length of insertion.

Catheterization, Central Venous↗
PubMed1997

The effect of aerosolized furosemide in infants with chronic lung disease.

To investigate whether aerosolized furosemide would improve pulmonary function in premature infants with chronic lung disease, we enrolled eight preterm ventilator-dependent infants in a cross-over, double-blind, placebo-controlled trial. Either aerosolized furosemide (2 mg/kg) or placebo (0.9% saline) was administered, and serial pulmonary function tests were performed before and at 1 and 2 h after each inhalation. After furosemide inhalation, static respiratory compliance increased significantly by 24.3% and 23.2% as percentage change from the baseline value at 1 and 2 h (p = 0.014 and 0.022, respectively). Also, tidal volume increased significantly by 33.8% and 28.7% at 1 and 2 h, respectively (p = 0.004 and 0.009). In contrast, no changes were observed in them after placebo inhalation. Total respiratory resistance was unchanged after both furosemide and placebo inhalation. There were no differences in urine volume in two groups. These data suggested that aerosolized furosemide improved pulmonary function in infants with chronic lung disease without excessive diuresis.

Administration, Inhalation↗
PubMed1997

Plasma thrombomodulin level in very low birthweight infants at birth.

OBJECTIVE: Plasma soluble thrombomodulin level reflects endothelial damage. The plasma thrombomodulin level at birth is increased in asphyxiated full-term infants. There is no report of plasma thrombomodulin level in premature infants. To determine the thrombomodulin level in premature infants and whether it might reflect endothelial damage, we examined the plasma thrombomodulin level in very low birthweight (VLBW) infants at birth. METHODS: Forty-five VLBW infants, of whom 14 had perinatal asphyxia complications, were recruited. As a control, 50 full-term infants without complications were also studied. Plasma thrombomodulin concentration, pH, base deficit, serum creatinine and D-dimer concentration, platelet count and fibrinogen concentration were measured within 1 hour after birth. RESULTS: There were significant differences in plasma pH, creatinine concentration, platelet count, antithrombin III activity and D-dimer concentration between VLBW infants and full-term infants. Plasma thrombomodulin concentration (39.0 (16.6-93.7) vs 27.0 (16.6-39.1) microg/L, p < 0.0001) and plasma thrombomodulin-to-serum creatinine ratio (0.82 (0.19-2.65) vs 0.47 (0.24-0.70) microg/micromol, p < 0.0001) were significantly higher in VLBW infants than those in full-term infants. By univariate analyses for all neonates, there were significant relations between plasma thrombomodulin concentration and gestational age, birthweight, plasma pH, creatinine concentration, platelet count and antithrombin III activity. A stepwise multiple linear regression model using the above variables as dependent factors showed only birthweight contributed significantly to plasma thrombomodulin concentration (plasma thrombomodulin concentration (microg/l) = 45.677-0.006 (birthweight; g), r2 = 0.323, p < 0.0001, n = 94). Plasma thrombomodulin concentration and plasma thrombomodulin-to -serum creatinine ratio in VLBW infants with asphyxia were higher than in those without asphyxia, but not significantly different (43.2 +/- 17.7 vs 38.3 +/- 8.5 microg/l and 0.92 +/- 0.60 vs 0.83 +/- 0.37 microg/micromol). CONCLUSION: Plasma thrombomodulin level in VLBW infants shows a high value at birth, and we consider the main factor responsible for this elevation may be endothelial damage or low clearance rate of thrombomodulin, which may be related to early gestational age.

Antithrombin III↗