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Biomedical subjects

H Mikawa

Publications and source records attributed to H Mikawa.

At least 109 records · Page 6Linked to original sources
PubMed1991

Human recombinant erythropoietin directly stimulates B cell immunoglobulin production and proliferation in serum-free medium.

The effect of human recombinant erythropoietin (Epo) on B cell responses was studied in a serum-free medium. Epo enhanced IgM production and thymidine uptake by a human IgM-producing lymphoblastoid cell line, CBL. This effect was specific to Epo since enhancement was blocked by anti-Epo antibody but not by control antibody. Among the various cytokines, interleukin-4 (IL-4) enhanced IgM production and thymidine uptake while IL-6 enhanced IgM production without affecting thymidine uptake. In contrast, other cytokines including IL-1 beta, IL-2, IL-5, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), or granulocyte/macrophage colony-stimulating factor (GM-CSF) were without effect. However, the enhancing effect of Epo is different from that of IL-4 or IL-6, since Epo effect was not blocked by anti-IL-4 antibody or anti-IL-6 antibody. Moreover, specific binding of Epo was detected on CBL cells. Epo also enhanced immunoglobulin (IgG, IgM and IgA) production and thymidine uptake by purified tonsil small resting B cells stimulated by Staphylococcus aureus Cowan strain I (SAC) or by large activated B cells. In contrast, Epo had no effect on unstimulated small resting B cells. These results indicate that Epo could directly stimulate activated and differentiated B cells and could enhance B cell immunoglobulin production and proliferation.

Antibodies, Monoclonal↗
PubMed1991

Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation.

BACKGROUND: To elucidate the pathophysiological significance of endothelin in pulmonary hypertension associated with congenital heart defects, we measured plasma endothelin-like immunoreactivity (ET-LI) concentrations by using radioimmunoassay in 18 patients with pulmonary hypertension (PH group; age, 6 months to 12 years) in comparison with 27 patients without pulmonary hypertension (non-PH group; age, 6 months to 12 years). METHODS AND RESULTS: Blood samples were obtained from the vena cava, right atrium, right ventricle, left or right pulmonary artery, and pulmonary vein or the pulmonary arterial wedge position (pulmonary venous blood) during cardiac catheterization. Plasma ET-LI concentrations in the PH group were significantly higher than those in the non-PH group at all sampling sites. In the PH group, plasma ET-LI concentration showed a significant increase between the right ventricle and pulmonary artery and between the pulmonary artery and pulmonary vein. The increment of plasma ET-LI concentrations from the right ventricle to the pulmonary vein was significantly larger in the PH group than in the non-PH group and was significantly correlated with pulmonary artery pressure. CONCLUSIONS: Plasma ET-LI concentrations were elevated in patients with pulmonary hypertension; the elevation was due to the increased production of ET-LI in pulmonary circulation, indicating the possible involvement of endothelin in the pathophysiology of pulmonary hypertension.

Blood Pressure↗
PubMed1991

Non-Menkes-type copper deficiency with regression, lactic acidosis, and granulocytopenia.

A 2-year-old girl with granulocytopenia developed fever followed by truncal ataxia and progressive neurologic regression. CT demonstrated symmetric low-density areas in the cerebral white matter. Sural nerve biopsy revealed axonal degeneration. Blood lactate levels were high, and serum levels of copper and ceruloplasmin and urinary excretion of copper were low. Cultured skin fibroblasts showed normal copper uptake. Treatment with oral copper administration normalized serum copper and ceruloplasmin levels, blood lactate levels, and granulocyte count. However, copper levels in the CSF were still low, and the patient showed no clinical improvement. We speculated that copper transport across the intestinal wall and across the blood-brain barrier was impaired.

Acidosis, Lactic↗
PubMed1991

Embryonal carcinoma of the testis after acute myelomonocytic leukemia: a case report.

A case of embryonal carcinoma of the testis after acute myelomonocytic leukemia is reported. The interval between the initial diagnosis of leukemia and the appearance of embryonal carcinoma was almost three years. Although the patient had received neither irradiation nor alkylating agents, the case is regarded as one of secondary malignancy. Possible contributing factors are discussed.

Adolescent↗
PubMed1991

Dibutyryl cyclic AMP induces formyl peptide receptor expression and chemotactic responses in a human eosinophilic cell line, EoL-1.

We investigated actin polymerization and the increase of cytosolic free calcium concentration ([Ca2+]i) in a human eosinophilic leukemia cell line, EoL-1, in response to stimulation with chemotactic factors; we also investigated the effect of dibutyryl cyclic AMP (dbcAMP) on the responses. EoL-1 cells under normal culture conditions did not show either actin polymerization or an increase in [Ca2+]i when stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP). Expression of formyl peptide receptors was not detectable on untreated EoL-1 cells, either. Dibutyryl cAMP induced the expression of formyl peptide receptors and the responsiveness to fMLP. The responsiveness of EoL-1 cells to the complement fragment C5a and platelet-activating factor (PAF) was also induced or enhanced by dbcAMP. The growth of EoL-1 cells was decreased and the proportion of cells in the G0/G1 phase of the cell cycle was increased by the treatment of EoL-1 cells with dbcAMP. The proportion of eosinophilic granule-containing cells and the content of eosinophil cationic protein (ECP) in EoL-1 cells was also increased when they were stimulated with dbcAMP for a longer period. The responsiveness of EoL-1 cells to fMLP, C5a, and PAF was shown to be regulated independently. EoL-1 cells and dbcAMP seem to be useful for examining chemotactic receptor expression and its signal transduction mechanisms.

Actins↗
PubMed1991

[99mTc-HMPAO SPECT in epileptic disorders in childhood].

Single photon emission tomography (SPECT) using Tc-99m-d,1-hexamethylpropylenamine oxime (HMPAO) was performed in two children with epileptic disorders during both sleeping and waking diurnal stages. Immediate postictal and interictal SPECT scans were obtained for a child with partial epilepsy. They demonstrated an interictal decrease in the regional cerebral blood flow (rCBF) and a more remarkable immediately postictal decrease in rCBF. The focus was in the same region of the SPECT for both interictal and postictal spikes. Another patient was diagnosed as having continuous spike-waves during slow sleep without epileptic seizures. Although SPECT during wakefulness showed no asymmetry, SPECT during sleep revealed decreased rCBF at the same location as the predominant area of diffuse epileptic discharges. We conclude that HMPAO SPECT is useful in investigation of the etiological mechanisms of seizures and epileptic discharges in epileptic disorders in childhood.

Age Factors↗
PubMed1991

Regional cerebral blood flow in relation to MRI and EEG findings in tuberous sclerosis.

To identify the focus of paroxysmal neuronal activity causing epilepsy in tuberous sclerosis (TS), the regional cerebral blood flow (r-CBF) in 19 patients with TS was assessed using single-photon emission computed tomography (SPECT) with I-123 iodoamphetamine (IMP), in correlation with serial interictal EEGs and organic changes observed on magnetic resonance imaging (MRI). There was a general irregularity of cortical IMP uptake and retention in TS, and two-thirds of the cerebral regions exhibiting high intensity in T2-weighted MRI images (cortical tubers) showed a decrease in r-CBF. In addition to in tubers, decreased r-CBF was observed in regions in which MRI was considered to indicate destruction of the normal cortex, atrophy or vascular abnormalities, although these areas did not consistently show epileptic changes in serial EEGs. Among the cortical regions which consistently showed epileptic foci in serial EEGs, none showed abnormal r-CBF without lesions on MRI. We conclude that IMP-SPECT is useful for visualizing the epileptogenic laterality in cases with bilateral MRI lesions and EEG epileptic changes, and to differentiate epileptogenic foci from electrophysiological propagated areas. However, regarding the severity of epilepsy, the MRI findings showed a better correlation than the IMP-SPECT findings did.

Adolescent↗
PubMed1991

Role of PAF and cytokines in the modulation of Fc epsilon RII/CD23 expression on human eosinophils.

IL-4 and gamma IFN profoundly modulate the expression of the cell surface and soluble Fc epsilon RII/CD23 molecule, which is a low affinity Fc receptor for IgE having regulatory activity on immune system. IL-4 is a general inducer of Fc epsilon RII/CD23 on B lymphocyte, monocyte/macrophage, and eosinophil lineages, while gamma IFN counteracts the enhancing effect of IL-4 on normal B lymphocytes. However, the effect of gamma IFN is more complex than that of IL-4. gamma IFN up-regulates those on monoblast cell line U937 and eosinophil cell line EoL. This differential regulation of Fc epsilon RII/CD23 on B cells and the other cell types may play important roles in immune system, as macrophages and eosinophils are critical cells in the allergic reactions. In addition to cytokines, we found that platelet activation factor (PAF) up-regulates the expression of Fc epsilon RII/CD23, whereas transforming growth factor-beta (TGF-beta) and glucocorticosteroid (dexamethasone) down-regulate it on U937 and EOL cells. Variable and strong effect of these factors on the expression of CD23/Fc epsilon RII may indicate the involvement of this receptor system in the allergic as well as immune reactions and possibly the pathophysiology of the allergic and immunological disorders.

Antigens, CD↗
PubMed1991

[Clinical evaluation of cefpirome in children].

Cefpirome (CPR, HR 810) was clinically evaluated for its efficacy and safety in 11 patients with ages from 4 months to 11 years with bacterial infection. The results obtained are summarized as follows. 1. CPR was administered to 6 patients with bronchopneumonia, a patient with pneumonia, a patient with tonsillitis, 2 patients with acute pharyngitis and a patient with suppurative parotitis at daily dosage levels ranging 55.5-91.7 mg/kg, divided into 3 using intravenous bolus injection or 30 minutes drip infusion. Clinical responses of the 11 patients were as follows: excellent; 8 patients, good; 2 patients, poor; 1 patient, hence the efficacy rate was 90.9%. 2. Neither clinical adverse reaction nor abnormal laboratory test value was observed except slight elevation of GOT and GPT in a patient and leukopenia in another. 3. MICs of CPR against 18 beta-lactamase producing strains isolated from patients were as follows. MIC against a strain of Staphylococcus aureus was 1.56 micrograms/ml, MICs against 3 strains of Klebsiella pneumoniae were less than 0.025 microgram/ml, those against 3 out of 5 strains of Enterobacter cloacae were less than 0.025 microgram/ml and those against the remaining 2 strains were 0.05 and 0.20 micrograms/ml. MICs against 2 out of 3 strains Acinetobacter lwoffi were 1.56 micrograms/ml, and that of the remaining 1 strain was 0.39 microgram/ml. MICs against 2 strains of Pseudomonas cepacia were 1.56 micrograms/ml. MICs against a strain of Pseudomonas putida and a strain of Citrobacter diversus were 0.78 and less than 0.025 microgram/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

Dermatophagoides pteronyssinus specific IgM antibody and its complement activation in children with bronchial asthma.

Western blotting analysis and ELISA were used to examine Dp specific IgM abs in the sera and sputa of bronchial asthmatic and non-atopic children. With Western blotting Dp specific IgM abs were detected binding diffusely to high molecular weight (greater than 65 kD) components of Dp extracts and from the intensities of the staining of the sera the asthmatic children were divided into two groups: an intensive staining and a faint staining group. The non-atopic children showed still fainter staining than the latter group. ELISA titers of Dp specific IgM abs in the intensive staining group were significantly higher than in the faint staining group and the non-atopic children (p less than 0.01). Dp specific IgM abs in sputa were also detected more intensively in asthma than in non-atopy by Western blotting. The hemolytic complement activities of the fresh sera were consumed when they were incubated with Dp extracts at 37 degrees C. The degree of consumption was significantly higher in the intensive staining group than in the faint staining group and the non-atopic children (p less than 0.05). High molecular weight fractions of Dp extracts were responsible for this complement inactivation. From these results we suspected that Dp specific IgM abs might react with high molecular weight components of Dp to induce complement activation by the classical pathway and might cause chronic inflammatory changes in the respiratory mucosa. This chronic inflammation might emphasize IgE mediated asthmatic reactions to cause late phase reactions or chronic asthma.

Animals↗
PubMed1991

Disodium cromoglycate (DSCG) selectively inhibits IgE production and enhances IgG4 production by human B cell in vitro.

The effect of DSCG on human IgE production in vitro was studied. DSCG selectively inhibited interleukin-4 (IL-4) induced IgE production by mononuclear cells (MNC) from normal donors without affecting IgM, IgA, IgG1, IgG2 or IgG3 production. In contrast, DSCG enhanced IgG4 production. To achieve this effect, DSCG must be added to the culture at the initiation and be present throughout the entire culture period. Interferon-gamma (IFN-gamma) also inhibited IL-4-induced IgE production, but IgG4 production was not affected by IFN-gamma. Monoclonal anti-IFN-gamma antibody blocked the inhibition of IgE production by IFN-gamma, but did not block the inhibition of IgE production by DSCG. DSCG also selectively inhibited spontaneous IgE production and enhanced IgG4 production by B cells from atopic patients in the presence of T cells and monocytes. These results indicate that there is a mechanism of IgE production inhibition which is not mediated by IFN-gamma. We also found that DSCG is an excellent reagent for the study of IgE and IgG4 regulation in vitro.

B-Lymphocytes↗
PubMed1991

Disodium cromoglycate enhances ongoing immunoglobulin production in vitro in human B cells.

The effect of disodium cromoglycate (DSCG) upon human immunoglobulin (Ig) isotypes and IgG subclasses production by purified B cells was studied. DSCG enhanced IgM, IgG1, IgG2, IgG3, IgG4 and IgA production in a dose-dependent fashion, while DSCG failed to induce IgE production at any concentrations tested by purified B cells. When B cells were separated into small resting and large activated B cells, DSCG failed to induce Ig production from small resting B cells in the presence or absence of Staphylococcus aureus Cowan strain I (SAC). In contrast, in large activated B cells DSCG significantly enhanced all types of Ig production (two-to threefold), especially IgG4 production (seven-to 11-fold), except IgE, which large B cells did not produce. The enhancement of IgG subclass production was not subclass switching, since DSCG failed to enhance IgG1 production in B cells depleted of surface IgG1+ cells (sIgG1+ cells). Similarly, DSCG did not enhance IgG2, IgG3 or IgG4 production from sIgG2-, sIgG3- or sIgG4- B cells, respectively, Interleukin-4 (IL-4) or interleukin-6 (IL-6) also enhanced Ig production except IgG4 from large activated B cells. The enhancing effect of DSCG was not mediated by IL-4 or IL-6 since anti-IL-4 or anti-IL-6 antibody failed to block the DSCG-induced enhancement. DSCG also enhanced IgG2 and IgM production from human B-cell lines GM-1500 and CBL, respectively. These results suggest that DSCG directly and preferentially stimulates activated B cells which are producing Ig and, in addition, enhances their Ig production.

B-Lymphocytes↗
PubMed1991

Stimulation of Ig production and growth of human lymphoblastoid B-cell lines by nerve growth factor.

The effects of nerve growth factor (NGF) on human lymphoblastoid B-cell lines were studied. NGF increased Ig production and proliferation by lymphoblastoid B-cell lines GM-1500, GM-1056 and CBL in a dose-dependent manner. As little as 0.01 ng/ml of NGF was effective. This effect was blocked by anti-NGF serum but not by control serum. Other cytokines, including interleukin (IL)-1 beta, IL-2, IL-4, IL-5, interferon (IFN)-alpha, IFN-beta, IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF), did not stimulate Ig production. These results indicate that, in addition to its neurotropic effect NGF also acts as B-cell stimulatory factor.

B-Lymphocytes↗
PubMed1991

[A double blind study of the effectiveness of ketotifen in preventing the development of asthma in atopic dermatitis patients].

Many asthmatic children have experienced atopic dermatitis in their younger days. As it is very difficult to cure childhood asthma we attempted to determine the anti-allergic drug effects in preventing the development of asthma by using ketotifen on atopic dermatitis patients. The study was designed as a placebo controlled double blind trial of 128 atopic dermatitis patients aged from 2-34 months. 91 patients were given complete analysis in the study, 33 patients were given only a safety rate and 4 patients were dropped. The 91 patients were followed for 52 weeks. Our primary finding was that the development of bronchial asthma was inhibited in the ketotifen group compared to the placebo controlled group with a statistically significant degree (p less than 0.001). We also found that clinical symptoms of atopic dermatitis were significantly improved in the ketotifen group (p less than 0.001). Only 5 patients complained of mild side effects.

Age Factors↗
PubMed1990

The effect of adenosine on the fluorescence responses of chlorotetracycline-loaded human polymorphonuclear leukocytes.

Chlorotetracycline has been used in human polymorphonuclear leukocytes as a probe to investigate the state of membrane-bound calcium. We examined the effect of adenosine on the fluorescence responses of CTC-loaded PMNs stimulated with the synthetic chemotactic peptide, formyl-methionyl-leucyl- phenylalanine. Adenosine inhibited the decrease in CTC fluorescence in a dose-dependent fashion and its effect was reversed by theophylline, an adenosine receptor antagonist. Removal of extracellular adenosine by incubating PMNs with adenosine deaminase abolished the effect of adenosine. These data suggest that adenosine inhibits the release of membrane-bound calcium in PMNs that normally occurs in response to chemotactic stimuli, acting via PMN surface adenosine receptors.

Adenosine↗
PubMed1990

Inhibition of both etoposide-induced DNA fragmentation and activation of poly(ADP-ribose) synthesis by zinc ion.

Treatment of a human promyelocytic leukemia cell line (HL-60) with etoposide for 3-4 hrs produced an extensive degradation of DNA. Agarose gel electrophoresis showed DNA fragmentation in a nucleosomal ladder pattern. Simultaneous addition of zinc ion (ZnSO4, 1 mM) inhibited DNA fragmentation, although the amount of DNA strand breakage introduced initially by etoposide did not change significantly as measured by the DNA unwinding assay. Furthermore, zinc ion abrogated both the activation of poly(ADP-ribose) synthesis and the morphologic changes characteristic of apoptosis by etoposide. These results suggest that zinc ion inhibits a metabolic process somewhere between initial DNA cleavage through an interference with type II topoisomerase and delayed degradation of cellular DNA to a nucleosome-like pattern.

Cell Line↗
PubMed1990

Involvement of the noradrenergic system in the seizures of epileptic El mice.

We studied the role of the noradrenergic system in the seizures of epileptic El mice. To this end, the anticonvulsant activity of adrenergic drugs was tested with a scoring method, and the binding of [3H]dihydroalprenolol, [3H]prazosin and [3H]yohimbine was evaluated in whole brains and various brain regions from stimulated and unstimulated El mice, and their maternal ddy mice. The seizures of El mice were inhibited by noradrenaline, phenylephrine, oxymetazoline, clonidine and yohimbine in a dose-dependent manner. These preventive effects of alpha-adrenoceptor agonists were antagonized by pretreatment with alpha-adrenoceptor antagonists. The preventive effect of yohimbine was reversed by pretreatment with clonidine or alpha-methyl-p-tyrosine, although the latter drug did not affect the anticonvulsant effect of clonidine. The binding of [3H]dihydroalprenolol was the same in the three groups of mice. More [3H]prazosin was bound in the cerebellum and striatum, and there were more [3H]yohimbine binding sites in the whole brain, cerebral cortex, hippocampus and brainstem of stimulated and unstimulated El mice than in the same areas of ddy mice. These findings suggest that up-regulated alpha 1- and alpha 2-adrenoceptors are involved in the inhibition of the seizures of El mice.

Animals↗