PubMed Health⌕ Search

Biomedical subjects

A Morikawa

Publications and source records attributed to A Morikawa.

At least 19 recordsLinked to original sources
PubMed1998

A new compound heterozygous mutation (W17X, 436 + 5G --> T) in the cytochrome P450c17 gene causes 17 alpha-hydroxylase/17,20-lyase deficiency.

A genetic disorder in cytochrome P450c17 results in 17 alpha-hydroxylase/17,20-lyase deficiency. In the present study, a Japanese patient with 17 alpha-hydroxylase/17,20-lyase deficiency underwent molecular analysis. The patient presented with complete female genitalia with a 46,XY karyotype, absent pubertal development, and hypertension. the exons and exon-intron boundaries of P450c17 genetic region were amplified and sequenced. DNA sequencing revealed a compound heterozygous mutation. One allele showed a G to A transition corresponding to a premature termination codon at tryptophane in codon 17 (W17X). The other allele showed a G to T substitution at the fifth nucleotide from the splice donor site in intron 2 (436 + 5G --> T). W17X was found in one allele of the father, and 436 + 5G --> T was found in one allele of the mother. A previous report presented a patient with 17 alpha-hydroxylase/17,20-lyase deficiency who was homozygous for W17X. However, the present case is a novel 436 + 5G --> T mutation. Reverse transcription-PCR analysis using total ribonucleic acid isolated from the testes of the patient revealed that an intron 2 donor site mutation caused abnormal splicing, such that exon 2 was spliced with intron 2. Skipping the exon alters the translational reading frame of exon 3 and introduces a premature termination codon. In semiquantitative analysis, the majority of the transcript for 436 + 5G --> T skips exon 2. The present findings indicate that in this patient, 17 alpha-hydroxylase/17,20-lyase deficiency was caused by the compound heterozygous mutation of exon and splice site mutation in cytochrome P450c17 gene.

Adolescent↗
PubMed1998

Diurnal variation of peak expiratory flow in children with cough variant asthma.

Cough variant asthma (CVA) is thought to be a variant form of asthma in which cough is the sole clinical manifestation of airways hyperresponsiveness, a characteristic feature of asthma. Another characteristic feature of asthma includes an increased diurnal variation of peak expiratory flow (PEF) compared to normal subjects. To examine whether diurnal variation of PEF might also increase in children with CVA, we have examined the degree of diurnal variation of PEF in these children (n = 7) by measuring peak flow serially for a week, and compared it with those in mild to moderate asthma (n = 17) and in control children without cough (n = 8). In control children without cough, the average value of the mean diurnal variation of PEF was 10.4 +/- 0.8%. In both groups of children with asthma and with CVA, there was a significant increase in the value (20.5 +/- 1.3% and 23.6 +/- 3.6%, respectively) compared to that in control children (p < 0.01 in both groups), although there was no significant difference between these 2 groups. These results show that mild, but significant airway obstruction is occurring in children with CVA, although clinical wheezing is not recognized. Serial measurements of diurnal variation of PEF may be helpful for the diagnosis of CVA in children.

Asthma↗
PubMed1997

Augmentation of lipopolysaccharide-induced thymocyte apoptosis by interferon-gamma.

The role of interferon (IFN)-gamma on thymocyte apoptosis in response to lipopolysaccharide (LPS) was investigated. The administration of LPS into mice induced marked apoptosis of thymocytes in vivo, but the simultaneous injection of anti-IFN-gamma antibody with LPS completely prevented thymocyte apoptosis. Pretreatment of mice with IFN-gamma markedly enhanced LPS-induced thymocyte apoptosis. Thymocyte apoptosis augmented by IFN-gamma occurred in the thymic cortex, and target cells undergoing apoptosis were CD4+8+ immature thymocytes. IFN-gamma itself did not induce thymocyte apoptosis in vivo and in vitro. IFN-gamma exhibited no synergistic action with effector molecules, such as tumor necrosis factor (TNF)-alpha and glucocorticoids. Further, it was shown that IFN-gamma did not enhance the susceptibility of thymocytes to apoptosis. Pretreatment of mice with IFN-gamma significantly augmented the serum TNF-alpha level and the serum cortisol level in response to LPS. Therefore, we suggest that IFN-gamma might augment LPS-induced thymocyte apoptosis through elevating serum TNF-alpha and cortisol levels.

Animals↗
PubMed1997

Nuclear ADP-ribosylation factor (ARF)- and oleate-dependent phospholipase D (PLD) in rat liver cells. Increases of ARF-dependent PLD activity in regenerating liver cells.

Two forms of phospholipase D (PLD) have been found to be present in nuclei isolated from rat hepatocytes by measuring phosphatidylbutanol produced from exogenous radiolabeled phosphatidylcholine in the presence of butanol. In nuclear lysates from either rat liver or ascites hepatoma AH 7974 cells, the PLD activity was markedly stimulated by a recombinant ADP-ribosylation factor (rARF) in the presence of the guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) and phosphatidylinositol 4, 5-bisphosphate. ATP and phorbol-12-myristate 13-acetate had no synergistic effect on this PLD activity. On the other hand, the nuclear PLD was stimulated by unsaturated fatty acids, especially by oleic acid. The ARF-dependent nuclear PLD activity was increased in the S-phase of the regenerating rat liver after partial hepatectomy and also was much higher in AH 7974 cells than in the resting rat liver. In contrast, the levels of the oleate-dependent PLD activity remained constant throughout the cell cycle in liver regeneration. The intranuclear levels of the stimulating proteins of the nuclear PLD activity, e.g. ARF, RhoA, and protein kinase Cdelta increased in the S-phase of the regenerating liver. These results suggested that the nuclear ARF-dependent PLD activity may be associated with cell proliferation.

ADP-Ribosylation Factors↗
PubMed1997

Lipoprotein glomerulopathy: a pediatric case report.

We report an 8-year-old girl with lipoprotein glomerulopathy who may have developed this condition as young as 4 years of age. To our knowledge this is the youngest reported case of this disease. Lipid studies of the patient and her family members revealed elevated concentrations of apolipoprotein E (apo E), the apo E phenotype E2/3, and the genotype E3/3. However, other families revealed no urinary abnormalities. Our findings suggest that an apo E abnormality may be responsible for the development of lipoprotein glomerulopathy. Genetic analysis of apo E is needed to clarify the pathogenesis.

Apolipoproteins↗
PubMed1997

The relationship between disturbed transit and dilated bowel, and manometric findings of dilated bowel in patients with duodenal atresia and stenosis.

To determine whether dilated bowel proximal to obstruction associated with duodenal atresia and stenosis is related to feeding problems after a surgical correction of obstruction, the authors reviewed retrospectively the degree of bowel dilatation and disturbed transit as well as other clinical features in 18 duodenal atresia and 12 duodenal stenosis patients. A multivariate analysis was conducted to determine the possible correlation among them. The authors also evaluated the physiological function of the dilated bowel in duodenal atresia and stenosis patients (n = 8) by manometry of dilated bowel. The results were as follows. (1) In multivariate analysis, using the degree of disturbed transit as a dependent variable and using other clinical features as independent variables, the presence of postoperative complication and the existence of bowel dilatation 2 weeks after the operation were risk factors for disturbed transit. (2) One or two episodes of phase 3 were found in six of eight measured patients during the recorded period. The most distinctive manometric finding was the low contraction amplitude of both phase 2 and phase 3. These results indicate that dilated bowel was related to disturbed transit during the postoperative period, and that the low contraction amplitude of the dilated bowel was the main pathophysiological feature. The tapering or plication of dilated bowel might be indicated in patients with a markedly dilated bowel.

Constriction, Pathologic↗
PubMed1997

A novel point mutation of thyroid hormone receptor beta gene in a family with resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is characterized by variable tissue hyporesponsiveness to thyroid hormone caused by mutations of thyroid hormone receptor beta (TRbeta) gene. We found a novel point mutation of the TRbeta gene in a family (F123) with RTH, a transition of a guanine to adenine at nucleotide 1215, which replaced the normal Met-310 with Ile. This substitution was found in only one allele of affected family members. In vitro transcription and translation of this mutant TRbeta demonstrated a 12-fold reduction of the affinity for triiodothyronine (T3) compared with the wild type TRbeta. Thyroid function tests were similar to a previously reported RTH family (F99) who had a different mutation in the same codon (Thr 310).

Adolescent↗
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

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↗
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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗