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Biomedical subjects

H Mikawa

Publications and source records attributed to H Mikawa.

At least 19 recordsLinked to original sources

[An experience with St. Jude medical prosthetic 19A-HP which resulted in restricted opening at an early stage after operation].

St. Jude medical hemodynamic plus series is positively used for aortic valve replacement (AVR) of small orifice because it can increase the orifice area by 26% compared with conventional prosthetic valves of the same size. We performed AVR with SJM 19A-HP on a patient having aortic stenosis with regurgitation using horizontal mattress suturing technique. The aortic orifice size was 18.9 mm at the preoperative measurement. The course after the operation was uneventful until 9 days after the operation when cinefluoroscopy revealed symmetrical restriction of opening of valve leaflets. We are now monitoring the clinical course at the patient has not developed any symptoms though the LV-Ao pressures gradient is 60 mmHg by Doppler echocardiography. As the restriction of valve leaflet opening was symmetrical, it is not likely that an excess of the ligature or remnant caused the restriction; structural problems of St. Jude medical prosthesis appear to be a more reasonable explanation. Since the orifice ring of this prosthesis is not reinforced, longitudinal forces applied to the hinge may alter the shape of the ring, thus restricting the movement of valve leaflets. In the present case, forced insertion of 19A-HP instead of more desirable 17-HP is considered to have caused longitudinal forces acting on the hinge.

Aged

[Epidemiological research on incidence of atopic disease in infants and children in relation to their nutrition in infancy].

Incidence and relative risk of atopic disease (atopic dermatitis; AD, bronchial asthma; BA, allergic rhinitis; AR) in Japanese infants and children in relation to their nutrition in infancy was analyzed from the data of the epidemiological survey which was conducted for 10,000 mothers of infants and children in 1993. A total of 4,610 replies were received: 2,714 from mothers of infants (12 months old) and 1,896 from mothers of children (2 years old). The subjects were allocated to following 3 groups based on their nutrition during first 3 months after birth; the breast-fed group (BF), the formula-fed group (EF), the mixed-fed group (MF). Incidence of atopic disease in BF, FF and MF was 23.5%, 22.2% and 21.8%, respectively and no statistical difference could be found among these 3 groups. AD was developed 17.0%, 14.4% and 13.9%; BA was 4.4%, 8.5% and 5.2%; AR was 4.9%, 6.5% and 5.8% in BF, FF and MF, respectively. Incidence of AD was significantly different between BF and MF (p < 0.01). Incidence of BA was also significantly different between BF and FF (p < 0.01). Risk of onset of BA and AR in FF was higher (adjusted odds ratio 2.2, 95% confidence interval 1.5-3.2 and adjusted odds ratio 1.5, 95% confidence interval 1.0-2.2, respectively) than that of BF controlled by age and family history with Cochran-Mantel-Haenzel test. With multiple logistic regression analysis, relative risk of the onset of BA in FF at the age of one year was 2.1, 95% confidence interval 1.2-3.5 and at the age of two years old was 2.5, 95% confidence interval 1.4-4.4. These results suggest that the breast-fed have certain suppression effects on incidence of bronchial asthma in infants and children.

Asthma

[Replacement of the aortic root with woven and knitted Dacron composite graft].

Some of the patients with annuloaortic ectasia or Stanford type A require aortic root replacement. If conventional Bentall procedure is employed in such cases, aortic root will become a cylindrical shape totally lacking sinus of Valsalva because the procedure utilizes a straight tube. The sinuses of Valsalva support an important role in opening and closing the valvar leaflets, and opening of the coronary arteries, together with the interleaflet triangles and the sinutubular junction. In this study, we performed aortic root replacement with composite graft which consisted of two types of graft including 30 mm Knitted Dacron Graft (Gelsoft) with different dilation rates and 30 mm Woven Dacron Graft (Hemashield) as well as bioprosthesis (27 mm Carpentier-Edwards), in order to reconstruct sinus of Valsalva. Post-operative angiography revealed an excellent diastolic coronary flow, as evidenced by proximal Knitted graft of 37 mm in diameter, distal Woven graft of 30.3 mm in diameter and Doppler flow DSVR (Diastolic/Systolic Velocity Ration) of 2.2 measured at the left coronary orifice. Since it is difficult to obtain homograft at present, this procedure would be worth trying during aortic root replacement.

Aged

[A epidemiologic study on the prevalence of the allergic diseases in school children in Kyoto City].

UNLABELLED: The prevalence of allergic diseases in school children in Kyoto City (17,906 children) was examined with the questionnaire which was prepared by the Study Group of Epidemiology of Allergic Diseases funded by the Ministry of Public Welfare in 1993. RESULTS: 1) The number of valid reply was 16,176 (reply rate 90.3%). The reply rate of each question was from 89.5% to 98.9% (average 95.7%). 2) The prevalence of bronchial asthma was 4.9% in the elementary school children, 3.5% in the junior high school children and 4.5% in total, and the prevalence in boys was higher than girls (ratio 1.6). The prevalence of wheezing was 6.5%, 2.7% and 5.5%, respectively, and the sex ratio was 1.2. 3) The prevalence of atopic dermatitis was 5.3% in elementary school children, 4.0% in junior high school children and 5.0% in total, and the prevalence in boys was lower than girls (ratio 0.87). 4) The prevalence of allergic rhinitis was 19.8% in elementary school children, 21.2% in junior high school children and 20.3% in total, and the prevalence in boys was higher than girls (ratio 1.3). 5) The prevalence of allergic conjunctivitis was 11.9% in elementary school children, 15.4% in junior high school children and 13.0% in total and the prevalence in boys was almost same as girls (ratio 0.98). 6) The prevalence of any allergic diseases was 32.2% in elementary school children, 31.7% in junior high school children and 32.1% in total and the prevalence in boys was higher than girls (ratio 1.2).

Adolescent

Survey of family history on allergy in 1-year-old and 6-year-old children.

A retrospective survey of a family history of allergy employing a special questionnaire for children was performed. The survey included 1-year-old (n = 267) and 6-year-old children (n = 410) with allergies as well as 1-year-old (n = 313) and 6-year-old children (n = 329) without allergies. An 'Allergy Risk Score' (ARS) for each subject was calculated according to the history of allergy in three family members: father, mother and a sibling. Each family member was scored as 2.0 (overt history of allergies), 1.0 (provable), 0.5 (possible) or 0 (absent), and the ARS of the subjects was calculated as the total of the family members' scores. The ARS of children in the allergy groups was statistically higher than that of the control groups in both age groups. The ARS increased with an increase in the odds ratio (an approximate value of the risk), especially in 6-year-old children. An ARS calculated on the basis of family history could be a useful and practical index for estimating the risk of allergy development in children, and may be helpful in predicting and preventing allergies in infants and children.

Child

Serum levels of interleukin 4 and soluble CD23 in children with allergic disorders.

UNLABELLED: In order to clarify the clinical significance of serum interleukin 4 (IL-4) levels, we measured serum IL-4 concentrations in allergic and non-allergic children using a highly sensitive sandwich ELISA. The limit of detection of the assay was 0.15 pg/ml in serum samples. Serum IL-4 was detected in 96.3% (53/55) of non-allergic controls, in 92.9% (183/197) of allergic children, in 70% (7/10) of cord blood samples and in 86.7% (26/30) of neonates. The IL-4 levels in sera from non-allergic controls were relatively constant during the ages examined and all samples were under 1.5 pg/ml. In allergic children, the serum levels of IL-4 were significantly elevated, particularly at age 13-24 months. The serum levels of IL-4 did not differ in children with different clinical manifestations of allergy, such as bronchial asthma, and atopic dermatitis. The serum level of soluble CD23 (sCD23) showed an age-dependent change in allergic and non-allergic children and was significantly higher in allergic than in non-allergic infants aged 7 to 12 months, but not in other age groups. There was no significant correlation among serum levels of IL-4, sCD23 and IgE. CONCLUSION: It is suggested that the measurement of serum IL-4 and sCD23 is helpful in the examination of allergic patients in infancy and early childhood, but neither the serum level of IL-4 nor sCD23 directly reflects in vivo IgE production.

Asthma

[Questionnaire survey on "The guidelines on diagnosis and treatment of asthma" edited by the Japanese Society of Allergology (1993)].

A questionnaire on the evaluation of "The Guidelines on Diagnosis and Management of Asthma" edited by the Japanese Society of Allergology in 1993 was sent to 586 physicians consisting of specialists authorized by the Japanese Society of Allergology and the board members of this Society, who treated patients with bronchial asthma. Of total 306 (52.2%) who responded, 177 (57.8%) answered the questions on adult asthma only, 65 (21.2%) on childhood asthma only and 52 (17.9%) on both adult and childhood asthma. In total, we had 229 respondents on adult asthma and 117 on childhood asthma. As a result, on drug therapy for chronic asthma, it was pointed out that the use of oral anti-allergics, oral steroids and inhaled beta-stimulants was excessive whereas the use of DSCG, inhaled steroids and long acting theophylline was slightly insufficient in both adults and children. On the management of acute episodes, the excessive use of beta-stimulants (inhaled, oral and injections) and the lack of the use of parenteral steroids and oxygen inhalation were pointed out in adults. The lack of oxygen inhalation also got a higher percent in children. Nevertheless, the guidelines were found to be highly regarded as a whole: "Very good" was 6.1% in adults (6.8% in children). "Appropriate" 38.0% (33.3%), "Almost appropriate" 52.0% (52.1%) and "Inappropriate" 3.9% (3.4%).

Adult

[Serum ECP level of infants of atopic dermatitis].

Forty-seven infants with atopic dermatitis (AD) were examined for ECP (eosinophil cationic protein) levels in sera at 3 to 4, 6 to 7, 12 and 18 months after birth. ECP levels in AD were significantly higher than those of control infants at every examination. The levels of ECP in AD were significantly correlated with the severity of dermatitis judged by a slightly modified version of the method of Businco et al. We concluded that ECP levels in sera are a useful marker for the severity of dermatitis in infants with AD.

Biomarkers

Molecular basis for developmental changes of GM-CSF gene inducibility in embryonal carcinoma cells.

In a previous report, we reported that the induction of GM-CSF gene in differentiated P19 cells results from the maturation of the transcriptional machinery. Here, we identified a cis-DNA element which confers the activation of GM-CSF gene in response to PMA/A23187 stimulation in differentiated state. Analysis of the 5'-flanking region between -113 and -60 revealed two elements responsible for promotion and one for inhibition, and the overall effects led to the activation of GM-CSF gene mainly through the sequence between -95 and -73. Using the oligonucleotide between -94 and -73 as a probe in gel retardation assays, we identified a DNA-binding protein, NF-GM-P19, the binding activity of which was induced after differentiation in response to PMA/A23187 stimulation. These results indicate that the induction of GM-CSF gene after differentiation results from the maturation of the transcriptional machinery which recognizes the sequence between -95 and -73.

Animals

Involvement of CD11b/CD18 in enhanced neutrophil adhesion by Fc gamma receptor stimulation.

Neutrophils showed a rapid and transient adhesion to immunoglobulin G (IgG)-coated plates compared with their adhesion to bovine serum albumin (BSA)-coated plates: the adhesion reached a peak after 15 min of incubation and then gradually returned to almost the basal state in 60 min. The addition of monomeric IgG or anti-Fc gamma RII monoclonal antibody (mAb) (IV.3) suppressed the increase in adhesion, whereas anti-Fc gamma RIII mAb (3G8) was hardly effective, indicating that the interaction of Fc gamma R, especially Fc gamma RII, with coated IgG is involved in the process. Adhesion was also blocked by cytochalasin B, suggesting that functional actin filament structures are crucial. Protein kinase inhibitors, erbstatin and genistein, inhibited the adhesion in a dose-dependent manner. The adhesion was inhibited by anti-CD11b (M1/70) and anti-CD18 (MHM23, TS1/18) mAbs. Moreover, neutrophils from a patient with complete leukocyte adhesion deficiency syndrome did not show increased adhesion to IgG-coated plates. The adhesion of neutrophils to fibrinogen- and BSA-coated plates was also increased when Fc gamma R was stimulated in the fluid phase with soluble aggregated IgG, which was also inhibited by anti-CD11b mAb. Stimulation of neutrophil Fc gamma R with soluble aggregated IgG enhanced the expression of CD11b in concert with the enhanced adhesion. These data collectively suggest that stimulation via Fc gamma R evokes a tyrosine kinase-dependent and actin filament-dependent intracellular signal that enhances the specific and nonspecific adhesive activity of neutrophils, presumably through the activation of CD11b/CD18.

Adult

Different mode of cell death induced by calcium ionophore in human leukemia cell lines: possible role of constitutive endonuclease.

The mechanism of cell death induced by calcium ionophore, A23187, was investigated in six human leukemia cell lines. Following exposure to 1 microM A23187, the myelogenous cell lines (HL-60, U-937, KG-1) underwent apoptosis within 3 h as determined by their morphology and DNA fragmentation assay. In contrast, T-lymphoblastic leukemia cell lines (Molt-4, Molt-3, CEM) revealed necrotic cell death after 24 h of incubation. However, an initial rise of intracellular free calcium concentrations and growth inhibition after treatment with A23187 were similar in the two cell types. We further showed that an endonuclease capable of mediating internucleosomal DNA fragmentation was constitutively expressed in the cytosol but not in the nuclei of the myelogenous cell lines, although this endonuclease was not detected in either the nuclei or the cytosol of the T-lymphoblastic cell lines. The activation of the endonuclease in myelogenous cells is calcium-independent and has an optimal pH of 7.5-9. It is inhibited by 1 mM zinc ion or 300 microM aurintricarboxylic acid. We propose that this constitutive endonuclease may be related to the susceptibility of myelogenous leukemia cell lines to apoptotic cell death.

Apoptosis

Age-related acute adriamycin cardiotoxicity in mice.

Myocardial mitochondrial function after acute adriamycin exposure was compared in infant and adult mice. Heart mitochondrial were isolated 48 h after an intraperitoneal injection of adriamycin. Concentrations of adriamycin in serum and heart tissue were not significantly different between infant and adult mice. Oxygen consumption (state 3 respiration), and respiratory control ratio (RCR) were studied polarographically. Enzyme activities in the respiratory chain [succinate-cytochrome c reductase (SCCR), NADH-cytochrome c reductase (NCCR), cytochrome c oxidase (CCO)], and adenine nucleotide translocase (ANT) were assayed. After saline injection (control), no significant differences were detected in state 3 respiration, RCR, and enzyme activity of ANT between infant and adult mice. The respective enzyme activities of SCCR, NCCR, and CCO in adult mice were significantly lower than those in infant mice. After adriamycin injection in adult mice, there were significant decreases in state 3 respiration (using glutamate and malate as substrates from 239 +/- 25 to 160 +/- 50 nanoatom O2/min/mg protein), RCR (using glutamate and malate as substrates from 7.2 +/- 1.0 to 4.4 +/- 1.4), and enzyme activities of SCCR (from 279 +/- 30 to 178 +/- 28 nmol/min/mg protein) and NCCR (from 331 +/- 43 to 237 +/- 30 nmol/min/mg protein), but there were no significant changes in infant mice. No significant changes in enzyme activities of CCO and ANT were found in either infant or adult mice following the administration of adriamycin. In conclusion, adriamycin is less toxic on the myocardial mitochondrial function in infant mice than in adult mice.

Acute Disease

Phenytoin reduces neonatal hypoxic-ischemic brain damage in rats.

We investigated the possible protective effect of phenytoin on hypoxic-ischemic brain damage in neonatal rats. Six-day-old rats underwent ligation of the left carotid artery followed by exposure to an 8% oxygen atmosphere for 2.5 hrs. We sacrificed the animals 72 hrs later and assessed the hypoxic-ischemic brain damage histologically. Phenytoin (50 mg/kg), administered intraperitoneally 1 hr before the hypoxia, reduced hypoxic-ischemic infarction in the cerebral cortex and striatum, and attenuated neuronal necrosis in the hippocampus. The plasma concentration of phenytoin after injection was 11.1 +/- 1.9 micrograms/ml (mean +/- S.E.M.) at 1 hr and 22.9 +/- 1.4 micrograms/ml at 4 hrs. Percent volumes of the infarction calculated by dividing the sum of damaged areas by the total area in serial coronal sections were 79 +/- 3% (mean +/- S.E.M.) in vehicle controls versus 13 +/- 6% in phenytoin-treated pups in the cerebral cortex, and 79 +/- 4% in vehicle controls versus 12 +/- 5% in phenytoin-treated pups in the striatum. We semiquantitatively investigated the hypoxic-ischemic change in 5 hippocampal areas: dentate gyrus, CA4, CA3, CA1, and subiculum, in the dorsal hippocampus. Pre-hypoxic treatment with phenytoin reduced hypoxic-ischemic damage in all areas examined. When phenytoin was administered immediately after the hypoxia, there was no difference between vehicle-injected controls and phenytoin-treated pups. These results demonstrate that phenytoin can reduce neonatal hypoxic-ischemic brain damage.

Animals

Developmental changes of GM-CSF gene inducibility in embryonal carcinoma cells.

Murine embryonal carcinoma (EC) P19 cells, a tissue culture model of early embryonic development, failed to produce cytokines, such as interleukin-3 (IL-3), IL-4, granulocytemacrophage colony stimulating factor (GM-CSF) and interferon-beta (IFN-beta) at the mRNA level. Differentiation induced by retinoic acid (RA) released this repression to produce some cytokines. GM-CSF and IFN-beta genes were expressed in response to PMA/A23187, poly(I):poly(C), IL-1 alpha, forskolin, or LPS stimulation in differentiated P19 cells, whereas IL-3 and IL-4 genes were not expressed. To elucidate the mechanism of the GM-CSF gene induction after differentiation, we transfected a series of 5' deletion mutants of the mouse GM-CSF promoter fused to the bacterial CAT gene. The 740-bp fragment of the 5'-flanking region mediated the positive response. Deletion analysis revealed that the 5' boundary region of the DNA element required for activation lies between positions -95 and -84 and the region upstream of position -95 appears inhibitory. These results indicate that the maturation of the transcriptional machinery after differentiation results in the activation of the GM-CSF gene.

Animals

A case of common variable immunodeficiency associated with cyclic thrombocytopenia.

A 12 year old boy was found to be deficient in immunoglobulins (Ig) A, G2 and G4, and common variable immunodeficiency was diagnosed. He also had cyclic thrombocytopenia at intervals of approximately 28-30 days. His bone marrow revealed normocellular with slightly decreased megakaryocytes. In vitro colony assays showed markedly imparied megakaryocytopoiesis, erythropoiesis and granulopoiesis. Platelet-associated IgG was elevated at his thrombocytopenic phase. Direct Coombs' test was repeatedly positive. Although not defined at present, we suggest the autoimmune nature of the disease.

Autoantibodies

Induction of apoptosis in childhood acute leukemia by chemotherapeutic agents: failure to detect evidence of apoptosis in vivo.

This study is designed to investigate whether apoptosis occurs in vivo in pediatric patients with acute leukemia during induction therapy. When patients with common acute lymphoblastic leukemia (cALL) and acute myeloblastic leukemia (AML) were treated with prednisolone (60 mg/m2/day, p.o. or i.v.) and etoposide (150 mg/m2/day, i.v.), respectively, the blast cell counts fell to below 30% and 5%, respectively, in 1 week. However, during this cytoreduction phase, neither morphologically apoptotic cells nor fragmentation of DNA derived from peripheral blast cells were detected at any preparations. On the other hand, cALL but not AML cells spontaneously undergo apoptosis following their culture in vitro. The addition of autologous serum instead of fetal calf serum substantially prevented apoptosis from occurring spontaneously in cALL cells. When cALL and AML cells freshly obtained from patients before therapy were treated in vitro with 10 mumol/l prednisolone and 20 micrograms/ml etoposide, respectively, these cells underwent apoptosis within 6 hours, as determined by a morphological and DNA fragmentation assay. These in vivo and in vitro findings suggest that, although anticancer drugs may induce apoptosis in vivo, these apoptotic cells cannot be detected due to their rapid removal from the circulation.

Adolescent

Inhibitor of nitric oxide synthesis reduces hypoxic-ischemic brain damage in the neonatal rat.

We evaluated the neuroprotective effect of the nitric oxide synthesis inhibitor, NG-nitro-L-arginine in a neonatal hypoxic-ischemic rat model. Unilateral hypoxic-ischemic injury was produced in the brain of 7-d-old rats using a combination of a common carotid artery ligation and a hypoxic (8% oxygen) exposure for 2.5 h. In our experimental condition, rectal temperatures did not differ between NG-nitro-L-arginine-treated and saline-injected pups. We killed the animals 72 h later and assessed the hypoxic-ischemic brain damage histologically. NG-nitro-L-arginine (2 mg/kg) administered intraperitoneally 1.5 h before hypoxia resulted in 77% reduction of the infarcted hemispheric volume and 87% reduction of the infarcted striatal volume compared to saline injected controls. NG-nitro-L-arginine given 1.5 h before the insult also significantly prevented hypoxic-ischemic damage in the five hippocampal structures examined, dentate gyrus, CA4, CA3, CA1, and subiculum. NG-nitro-L-arginine administered immediately after hypoxia did not prevent hypoxic-ischemic brain damage. These results indicate that nitric oxide plays a key role in producing neonatal hypoxic-ischemic brain damage.

Animals

Effect of dibutyryl cyclic AMP and interferon-gamma on Fc gamma receptor expression on eosinophils.

We studied the effect of dibutyryl cyclic adenosine-3',5'-monophosphate (dbcAMP) and several cytokines on the expression of IgG Fc receptor subclasses (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) and low-affinity IgE Fc receptors (Fc epsilon RII/CD23) on peripheral eosinophils and on eosinophils differentiated in vitro from cord blood mononuclear cells by interleukin 5 (IL-5). These eosinophils expressed Fc gamma RII, and few, if any, Fc gamma RI and Fc gamma RIII as determined by flow cytometry with specific monoclonal antibodies. dbcAMP enhanced the Fc gamma RII expression, but did not induce the Fc gamma RI and Fc gamma RIII expression. Interferon-gamma (IFN-gamma) enhanced Fc gamma RII expression at the same degree as did dbcAMP. IFN-gamma also induced Fc gamma RIII expression on peripheral eosinophils but not on eosinophils grown in the presence of IL-5. Eosinophils grown in the presence of IL-5 showed a relatively immature phenotype, determined by electron microscopy and the low content of eosinophil cationic protein. Contrary to its enhancing effect on Fc gamma RII expression, dbcAMP suppressed the IFN-gamma-induced Fc gamma RIII expression on peripheral eosinophils. Other cytokines examined did not show any effects on Fc gamma R expression. Fc epsilon RII/CD23 expression was neither detected nor induced. These results indicate that expression of Fc gamma RII and Fc gamma RIII on eosinophils is regulated differently and that cAMP and IFN-gamma play important roles in the regulation of Fc gamma R expression.

Blood Proteins