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Biomedical subjects

A Morikawa

Publications and source records attributed to A Morikawa.

At least 127 records · Page 7Linked to original sources

Plasma thrombomodulin level in newborn infants with and without perinatal asphyxia.

To determine whether vascular endothelial damage occurs in neonates with asphyxia, we examined the plasma thrombomodulin level at birth in infants with and without asphyxia. The plasma thrombomodulin concentration in 11 asphyxiated infants was significantly elevated compared with that in 48 infants without asphyxia (38.1 vs 27.0 micrograms/l, p < 0.0001). The plasma thrombomodulin-to-serum creatinine ratio was also significantly elevated (0.62 vs 0.48 microgram/mumol, p = 0.0005). The plasma thrombomodulin concentration and the plasma thrombomodulin-to-serum creatinine ratio in infants without asphyxia did not differ between the two types of delivery: normal vaginal delivery and elective caesarean section. Stepwise regression analysis showed the serum D-dimer concentration, plasma pH and serum creatinine concentration were significant independent variables for plasma thrombomodulin concentration, whereas base deficit, platelet count, fibrinogen concentrations and antithrombin III activity were not. Our data suggest that vascular endothelial damage might occur in asphyxiated infants.

Antithrombin III↗

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↗

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↗

Effect of maturation on allergen-induced airflow obstruction and airway plasma exudation in sensitized guinea pigs.

Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturation on airway responses provoked by allergen challenge [ovalbumin (OA) 0.05, 0.15 and 0.5 mg/kg i.v] in passively sensitized immature (190 +/- 2 g: 2 weeks old) and adult guinea pigs (566 +/- 16 g: 13 weeks old). In both groups of animals, we measured both lung resistance (RL) to monitor airflow obstruction and extravasation of Evans blue dye, to quantify airway plasma exudation. Immature guinea pigs required a larger dose of OA at the challenge to induce a significant increase in RL and extravasation of Evans blue dye compared with adult guinea pigs. In addition, immature animals responded less to the lower doses of OA than adults. Pretreatment with pyrilamine, an antihistamine, suppressed the increase in RL in immature animals, whereas the remaining component of the increase in RL was seen in adult animals. Intravenous allergen challenge causes less airflow obstruction and airway plasma exudation in immature than in adult guinea pigs. Allergen-induced airflow obstruction is mediated mainly via histamine in immature animals, whereas this may not be the case in adult animals.

Age Factors↗

Role of tyrosine kinases in human eosinophil degranulation.

Degranulation of eosinophils and subsequent release of toxic granule proteins play a key role in allergic diseases such as bronchial asthma. However, little is known about the intracellular signaling mechanism of eosinophil degranulation. In this report, we investigated the role of protein tyrosine kinases (PTK) in the degranulation of human peripheral blood eosinophils. Stimulation of eosinophils with Sepharose beads coated with secretory IgA (sIgA) or IgG triggered the phosphorylation of tyrosine residues in several proteins, including 50-65, 73, 78, 100, 105 and 113 kD. In addition, IgG-coated beads induced a rapid increase in the tyrosine kinase activity of src-like PTK, Fgr. The tyrosine kinase inhibitors, genistein and herbimycin A, inhibited both the tyrosine phosphorylation and degranulation responses of eosinophils induced by sIgA- or IgG-coated beads. In contrast, eosinophil degranulation induced by phorbol myristate acetate was not affected by genistein. These findings suggest that a PTK-dependent signaling pathway plays an important role in triggering the eosinophil degranulation induced by immobilized immunoglobulin.

Benzoquinones↗

Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma.

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0 +/- 0.8 yr) with a history of EIB participated in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo (0.9% saline) according to a double-blind, randomized, crossover design, and underwent an exercise challenge test 15 min after the pretreatment. Inhaled indomethacin significantly attenuated EIB. The mean maximal percent decrease in FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced the mean maximal decrease in arterial oxygen saturation after exercise (p = 0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in the airways may be a mechanism involved in the protective potency of inhaled indomethacin.

Administration, Inhalation↗

Effect of influenza A virus infection on acid-induced cough response in children with asthma.

Although it is well-known that some types of respiratory viral infections cause airway hyperresponsiveness in humans, the effect of viral infection on the cough threshold in asthmatics is not known. We, therefore, evaluated the effects of naturally-acquired influenza A virus infection on the cough threshold to inhaled acid in children with asthma. Twelve children with asthma (9 boys and 3 girls, mean +/- SEM age of 10.8 +/- 0.6 yrs), who had naturally-acquired influenza A virus infection in winter (January-February, 1992) during an epidemic of influenza A (H1N1), were enrolled in this prospective, uncontrolled study. All patients underwent acetic acid (AA) inhalation challenge 2, 4 and 6 weeks after the influenza infection. The cough threshold values (the lowest concentrations of AA eliciting coughs) after 2, 4 and 6 weeks of the illness were 3.7 +/- 0.9, 5.3 +/- 1.0 and 8.1 +/- 1.4% (mean +/- SEM), respectively. Cough threshold values 4 or 6 weeks after the illness improved significantly over that at 2 weeks (p < 0.05 and p < 0.01, respectively). In contrast, baseline forced expiratory volume in one second did not change throughout the study. These results indicate that influenza A virus infection attenuates the cough threshold independently of airway obstruction in children with asthma. The enhanced cough response following virus infection is probably mediated by damage to the airways epithelium.

Acetic Acid↗

Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation.

Most cases of congenital nephrogenic diabetes insipidus (NDI) are inherited in an X-linked manner, which is due to the mutations of the vasopressin type 2 receptor (V2R) gene. However, recent reports have presented female NDI patients with heterozygote V2R gene mutations. The mechanism of inheritance was thought to be skewed X-inactivation. We present a family with congenital NDI. Three male members were diagnosed with NDI, and examination of their V2R gene revealed a G inserted at nucleotide 804 of the open reading frame. Three female individuals display different degrees of symptoms of NDI, and all of them possess both the normal and abnormal genes. The X-inactivation patterns of the female members were investigated via the detection of methylated trinucleotide repeat in the human androgen receptor gene. The grandmother showed extremely skewed methylation of one X chromosome, and the mother revealed moderately skewed methylation. The daughter of the grandmother's sister, who has no symptoms of NDI, showed random methylation. The highly skewed X-inactivation pattern of the grandmother suggests that her NDI phenotype is caused by dominant methylation of the normal allele of V2R gene.

Adult↗

Relationship between concentration of serum leptin and fetal growth.

The serum leptin concentration reflects the amount of adipose tissue in the body. Although fat deposition in the fetus in the third trimester markedly increases, the role of leptin during pregnancy has not been clarified. In the present study, whether or not the serum leptin concentration correlates with growth in utero was investigated, in addition to how leptin levels change in the first few days after birth. One hundred sixteen Japanese infants were divided into term (n = 91) and preterm groups (n = 25). Term infants were divided into 3 subgroups: birth weight appropriate for gestational age (AGA) (n = 44), birth weight large for gestational age (LGA) (n = 28), and birth weight small for gestational age (SGA) (n = 19). Longitudinal changes in the concentration of serum leptin after birth were examined in 48 infants. The serum leptin concentration was determined by RIA. No significant difference in leptin levels between cord sera and infants' sera obtained within the first 6 h of life (n = 28) was observed. Within the first 6 h of life, the concentration of serum leptin in LGA infants (12.8 +/- 10.2 ng/mL) and SGA infants (1.6 +/- 1.1 ng/mL) was significantly higher and lower, respectively, than that in the AGA infants (4.4 +/- 3.0 ng/mL) (P < 0.01). A significant positive correlation was found between the leptin concentration within 6 h of life and birth body weight (r = 0.59, P < 0.01). After birth, the concentration of leptin in LGA and AGA infants significantly decreased to the level in SGA infants within 72 h [corrected] of delivery (P < 0.05). After 72 h [corrected] of life, no significant differences in the concentration of leptin were observed among the three groups, and low levels continued to 7 days of age. These findings indicate that serum level of leptin correlates with fetal body weight gain.

Adult↗

Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM.

One form of maturity-onset diabetes of the young, MODY3, is characterized by a severe insulin secretory defect, compared with MODY2, a glucokinase-deficient diabetes. It has recently been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 alpha cause MODY3. Because of the rapid progress to overt diabetes and the high prevalence of required insulin treatment in patients with MODY3, we screened the HNF-1 alpha gene for mutations in Japanese subjects with IDDM. Ten exons and flanking introns of the HNF-1 alpha gene in these subjects were amplified by polymerase chain reaction and direct sequencing of the products. Mutations were identified in three (5.5%) of the 55 unrelated subjects with IDDM. A missense mutation of R272H (replacement of Arg by His in codon 272) in the DNA binding domain of HNF-1 alpha was found in a subject who developed IDDM 1 year after diagnosis of NIDDM at 8 years of age. A frameshift mutation of P291 fsinsC (insertion of a C in a polyC tract around codon 291 for Pro), which would generate a mutant truncated protein of 340 amino acids, was found in a subject who started insulin treatment when hyperglycemia and ketonuria were noticed at 13 years of age. A missense mutation of R583G (replacement of Arg by Gly in codon 583) in the transactivation domain of HNF-1 alpha was found in a subject with sudden-onset IDDM at 20 years of age. None of these mutations were present in 100 nondiabetic subjects (200 normal chromosomes). These results indicate that the HNF-1 alpha gene defects could lead to the development of not only early-onset NIDDM but also IDDM, implicating the importance of subclassification of HNF-1 alpha-deficient IDDM from a classical type of autoimmune-based IDDM in Japanese.

Adolescent↗

Roxithromycin attenuates acid-induced cough and water-induced bronchoconstriction in children with asthma.

In the present study, we evaluated the effect of roxithromycin, a semisynthetic macrolide antibiotic, on the cough response to inhaled acetic acid (AA) and on the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma. Ten hospitalized asthmatic children (8 boys and 2 girls, mean +/- SEM age 12.6 +/- 0.4 years) were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. All the patients underwent AA inhalation challenge before and 2, 4, and 8 weeks after the administration of roxithromycin. Seven of the 10 patients, who had a fall in FEV1 of at least 20% after UNDW inhalation, underwent UNDW inhalation challege at the same time. The cough threshold values, the lowest concentrations of AA eliciting coughs, and UNDW provocative dose producing a 20% fall in FEV1 (UNDW PD20) values 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05). No significant change was observed in baseline FEV1 or serum theophylline concentrations throughout the study. These results support the notion that administration of roxithromycin may have favorable results in the treatment of childhood asthma.

Acetic Acid↗

Molecular analysis of minimally differentiated acute myeloid leukemia with chromosome 16 inversion.

We report a 3-year-old girl with minimally differentiated acute myeloid leukemia and chromosome 16 inversion (inv 16). Inv 16 is generally associated with acute myelomonocytic leukemia with dysplastic eosinophils in the bone marrow (AML-M4Eo). Recently, molecular analysis showed that a fusion gene is generated by this inversion between the CBFB gene on the q arm and the MYH11 gene on the p arm. Using reverse transcriptase-polymerase chain reaction analysis, we tried to detect CBFB/MYH11 chimeric mRNA in blasts from our patients, however, were unable to detect any chimeric mRNA in the blasts: The absence of CBFB/MYH11 transcripts in this case suggests that rare chimeric products might be formed as a result of inv 16 that could not be detected by the primer sets used in this study. Another possibility is that different genes are rearranged on the chromosome 16 with the inv 16. More detailed molecular analysis of this case might be necessary in order to elucidate these possibility. Analyzing leukemias with inv 16 which do not have a typical CBFB/MYH11 chimeric mRNA might lead to understanding an alternative pathogenesis for acute leukemia with inv 16.

Acute Disease↗

[Usefulness of exercise electro-cardiography in a THP (Total Health Promotion Plan)].

We conducted ergometer exercise electrocardiography (ergometry) on 3,477 subjects in a THP (Total Health Promotion Plan). One hundred cases in which abnormal findings were detected by ergometry were analyzed. In the hundred cases there were 3 patterns: abnormal ST change, 50 cases; abnormal reaction, 22 cases; and extreme increase in blood pressure, 28 cases. Electrocardiograms (ECG) in 78 of these 100 cases indicated no abnormalities. Of the 31 subjects who underwent further examinations, in 18 cases abnormal findings were detected, and further observation or treatment was necessary. They were over two thirds of the 26 cases requiring observation or treatment on further examination. In other words, exercise electrocardiography revealed more than 3 times as many problem cases as electrocardiography only. One hundred and four cases were analyzed, and among them abnormal findings on ECG made further examination or treatment necessary. Of 68 subjects with an abnormal ECG and who needed to undergo exercise electrocardiography, 51 (75%) had no need to undergo further examinations, because there were no abnormal findings on ergometry in the THP. Of the 104 subjects who underwent ECG examination at rest, 51 no longer needed to waste time, effort and expense on further medical evaluation. Ergometry in a THP serves as a medical check and as a means to decide the strength of exercise before the initiation of exercise training, which is very important in preventing coronary artery disease, rather than in detecting the disease. Ergometry is expensive and it takes a lot of time and labor, but it is necessary in ensuring the safety of exercise training and in prescribing proper exercise. This analysis has shown that ergometry in THP is very useful and cost effective in improving the accuracy of health examinations.

Adult↗

Differential release of endotoxin from Pseudomonas aeruginosa treated with beta-lactam antibiotics and its effect on the lethal activity.

The relationship between the level of endotoxin released from Pseudomonas aeruginosa by exposure to beta-lactam antibiotics and the lethal activity against D-galactosamine (D-GalN)-sensitized mice was examined. In vitro treatment of P. aeruginosa with imipenem (IPM) exclusively caused low-level release of free endotoxin, which was not lethal for D-GalN-sensitized mice. Treatment with other beta-lactam antibiotics, such as ceftazidime (CAZ), meropenem (MEPM) and cefozopran (CZOP) caused high-level release of free endotoxin and it exhibited the lethal action against D-GalN-sensitized mice. This study demonstrated close association of free endotoxin released by antibiotic treatment with the lethal activity.

Animals↗

Effect of age, height, and prechallenge respiratory resistance on bronchial hyperresponsiveness in childhood asthma using the forced oscillation technique.

To evaluate the effects of age, height and prechallenge respiratory system resistance (Rrs) on bronchial responsiveness to methacholine inhalation (BRm) as measured by the oscillation technique in children with mild asthma, we studied BRm in 92 atopic children aged from 8 to 13 years (mean +/- SD, 10.5 +/- 1.7 years). Inhalation challenge was performed by administering progressively doubling doses of methacholine, until a twofold increase in Rrs from baseline had been reached. The minimum cumulative dose of methacholine (Dmin) at which Rrs deviated from baseline was identified by the point of deflection of the continuously recorded Rrs tracing. The Dmin represented the amount of methacholine which elicited BRm. By using single-regression analysis, height was negatively correlated with Rrs (p < 0.001). Height was positively and Rrs was negatively correlated with age (p < 0.001 and p < 0.001, respectively). Furthermore, height and age were correlated with Dmin (p < 0.001 and p < 0.001, respectively), but prechallenge Rrs was not correlated with Dmin (p > 0.1). To minimize the effect of height and prechallenge Rrs on BRm, the relationships between Dmin and age was studied in a subgroup with a narrow range of heights (135-155 cm, n = 32), and a narrow range of prechallenge Rrs (5.0-6.9 cmH2 O/L/s, n = 42); there remained a statistically significant correlation between Dmin and age in the groups with comparable heights (p = 0.026) and Rrs (p = 0.003). These data suggest that the BHR in childhood asthma may be affected by height and age when measured by the oscillation technique. Considering the many advantages of the oscillation method, this technique may be very suitable for measuring BHR in childhood asthma.

Administration, Inhalation↗