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Biomedical subjects

H Mikawa

Publications and source records attributed to H Mikawa.

At least 163 records · Page 9Linked to original sources

Interferon and (2'-5')oligoadenylate enhance the expression of low affinity receptors for IgE (Fc epsilon R2/CD23) on the human monoblast cell line U937.

The regulation of low affinity IgE receptor (Fc epsilon R2/CD23) expression on the human monoblast cell line U937 was examined by an anti-Fc epsilon R2/CD23 monoclonal antibody (H107) and the cDNA probe for Fc epsilon R2/CD23. Alpha interferon (IFN-alpha) and its intracellular mediator, (2'-5')oligoadenylate (2, 5-A), induced Fc epsilon R2/CD23 expression on U937 with no significant increase of the Fc epsilon R2/CD23 mRNA. PMA and IFN-gamma increased both surface Fc epsilon R2/CD23 expression and the Fc epsilon R2/CD23 mRNA levels. IFN-alpha effectively induced 2, 5-A synthetase activity in U937 cells, whereas IFN-gamma induced little. The results suggest that the mechanisms of enhancement of Fc epsilon R2/CD23 expression on U937 cells by IFN-alpha and IFN-gamma are different and that 2, 5-A may play an important role in the Fc epsilon R2/CD23 expression on U937 cells induced by IFN-alpha.

2',5'-Oligoadenylate Synthetase↗

Developmental changes of plasma ganglioside concentration during the neonatal period.

We investigated the developmental changes of plasma ganglioside concentration during the neonatal period. The mean plasma ganglioside concentration at birth was 8.22 +/- 3.70 nmol lipid-bound sialic acid (LBSA)/ml, significantly lower than the value in adults (12.05 +/- 1.36 nmol LBSA/ml, P less than 0.02). However, it increased rapidly early in the neonatal period and reached its maximum level at 14 days of age (16.25 +/- 6.04 nmol LBSA/ml), which was higher than that of adults (P less than 0.05); then it decreased slowly to the adult level at one month of age. The mean plasma ganglioside concentration in preterm infants (gestational age less than 37 weeks) was 6.65 +/- 3.35 nmol LBSA/ml, somewhat lower than that of fullterm infants (gestational age greater than or equal to 37 weeks, 9.90 +/- 3.39 nmol LBSA/ml, P less than 0.02) at birth. After birth, it increased much more rapidly in preterm infants and there was no significant difference between these two groups at 5 days of age. Plasma ganglioside concentration at birth increased gradually in correlation with gestational age. Our investigations show that plasma ganglioside concentration may reflect the development and maturation of the central nervous system to some degree, at least early in the neonatal period.

Adult↗

Landau-Kleffner syndrome. EEG topographic studies.

Spectral and historical topographic mapping of EEG was done on 2 siblings with Landau-Kleffner syndrome. The clinical features of the elder sister were acquired aphasia developed at the age of 5, followed by convulsions a year later, and those of the younger brother were progressive ataxia, hemiparesis, urinary incontinence and convulsions at the age of 4 years and 10 months, followed by acquired aphasia a year later. The most prominent spectral mapping features were high spectral powers of delta, theta and alpha waves over the fronto-centro-parietal area. The power of alpha and beta wave bands, reflecting sharp or spike waves, varied spatio-temporally over the central, parietal, temporal and frontal areas. The historical mapping revealed variabilities of paroxysmal discharges in modes of propagation. These results suggested that electrophysiological dysfunction of the fronto-centro-parietal areas associated with markedly unstable paroxysmal discharges is the main feature of Landau-Kleffner syndrome.

Aphasia↗

Evaluation of production and characterization of monoclonal antibodies to human IgG of four subclasses.

Human IgG of four subclasses, semi-purified from pooled human serum by a series of DEAE ion exchange and protein A affinity chromatographies, were used as immunogens and initial screening antigens to produce subclass-specific and -restricted monoclonal antibodies (McAbs). These McAbs were bound to CNBr-activated Sepharose 4B and utilized in immunoaffinity chromatography to prepare four polyclonal human IgG subclasses of satisfactory purities, which were then used as final screening antigens. Subclass-specific McAbs thus chosen were further evaluated for subclass- and especially allotype-specificity using a panel of monoclonal IgG myeloma proteins with representative Gm markers for each subclass in micro enzyme-linked immunosorbent assay (ELISA). A total of 10 clones of subclass-specific McAbs (one for anti-IgG1, three anti-IgG2, two anti-IgG3, four anti-IgG4) were established. Among them, IgG2-specific clones of HG2-30F and HG2-56F, IgG3-specific HG3-7C and HG3-32C, and IgG4-specific HG4-53G McAbs were superior to the corresponding specificity standard McAbs chosen by the Human Immunoglobulins Subcommittee of the WHO/International Union of Immunological Societies (IUIS) in 1985. As allotype-specific McAbs, HG1-1E for G1m(az) and HG3-3B for G3m(b) were obtained. In micro ELISA of this study as well as all protocols of the previous WHO/IUIS collaborative study, antigens (myeloma IgG subclasses) were immobilized or fixed to a solid phase, resulting in possible variations in their epitope expressions. We developed a new assay system, micro radioimmunoassay (RIA), in which reactivities of McAbs against free IgG subclasses in solution can be evaluated. HG2-30F, having extremely high reactivities to coated IgG2 in micro ELISA, remarkably reduced its reactivities to free IgG2 in solution in micro RIA. Two other clones also showed some different reactivities in micro RIA and micro ELISA. We believe that this micro RIA is valuable for evaluation of McAbs reactivities against native human IgG subclasses in solution.

Animals↗

Y chromosome specific DNA probe in the diagnosis of a patient with mos 45,X/46,XYnf.

In a patient with mos 45,X/46,XYnf, the diagnosis was confirmed with a Y chromosome-specific DNA probe, Y-190. The patient was a phenotypic female without Turner syndrome stigmata other than short stature. She showed some evidence of virilization and high serum testosterone. Her peripheral blood karyotype was mos 45,X/46X, +mar. Although this marker chromosome resembled a Y chromosome, there was no quinacrine bright region on its long arm. Southern blot analysis of her peripheral blood mononuclear cell DNA with Y-190 as a probe showed strong hybridization with this probe. Gonadectomy was performed, and bilateral gonadoblastomas were found.

Adolescent↗

Maturational study of short-latency somatosensory evoked potentials after posterior tibial nerve stimulation in infants and children.

SSEPs produced in response to PTN stimulation were studied in 41 normal infants and children from 4 months to 16 years in age. SSEPs were recorded on the scalp with reference electrodes attached to the contralateral knee, shoulder and earlobe. Four positive SSEPs, PI, PII, PIII and PIV, named in order of appearance, and one negative SSEP, N0, were recorded as FFPs on the scalp with the cKn reference. Following these FFPs, the cortical component P1 which corresponded to P37 in adults was recorded. Preceding P1, another negative wave, N1, could be recognized solely at Cz' mainly at the onset of P1. P1 and N1 could be identified in all children with derivations with noncephalic references, although they could not be identified in 5 of 41 children with a Cz' - Fpz derivation. PI, bilobed in configuration, was considered to originate at the sacral plexus or entry to the spinal canal. PII was the least reproducible potential and was considered to originate at the dorsal root, dorsal horn or conus medullaris. PIII, PIV and N0 were considered to originate at the cervical cord, brain stem and thalamus, respectively. With the peak latencies of PI, PII, PIII, PIV, N0, N1 and P1, the RV was calculated in order to eliminate the influence of body height. The RV of the later appearing components leveled off in the older age categories. The RV of P1 reached a steady level at 3 years of age. RVs of PII and PIII appeared to level off by the age of 6 years. The RV of PIV leveled off by the age of 9 years. RVs of N0 and N1 leveled off by the age of 12 years, and that of P1 decreased until over 12 years of age. Furthermore, to eliminate the influence of naturation in the peripheral nerves, the RV was obtained from PI-PIV, PI-P1, PIV-P1 and N1-P1 interpeak latencies. The RVs of these 4 interpeak latencies all decreased until over 12 years of age. Accordingly, the maturation of afferent conduction in the central nervous system after PTN stimulation appeared to be complete after 12 years of age.

Adolescent↗

Soluble low affinity Fc receptors for IgE in the serum of allergic and nonallergic children.

IgE-binding factors are thought to have regulatory activity in in vitro IgE synthesis. To obtain evidence of the participation of IgE-binding factors in in vivo IgE synthesis, the serum level of low affinity Fc receptors for IgE (sFc epsilon RII) (IgE-BFs) was examined in 41 nonallergic children and in 37 allergic children whose serum IgE levels were significantly higher than those of nonallergic children. The serum level of sFc epsilon RII showed a marked age-dependent variation. It was highest in infants and then decreased gradually with age. The serum level of sFc epsilon RII in allergic children was significantly higher than that of nonallergic children in early childhood (1128.0 +/- 323.8 vs 777.3 +/- 227.0 pg/ml, p less than 0.01 in infants (less than 1 y) and 851.8 +/- 270.0 vs 579.4 +/- 197.1 pg/ml, p less than 0.05 in children aged 1-2 y) but not in older children (3-15 y). Three allergic infants (less than 1 y) with serum sFc epsilon RII levels higher than the mean + 1 SD (1451.8 pg/ml) of all allergic infants (less than 1 y) had serum IgE levels (geometric mean 125.9 IU/ml) significantly higher than the other seven allergic infants (less than 1 y) (geometric mean 5.6 IU/ml, p less than 0.05). A close positive correlation between the serum level of sFc epsilon RII and the absolute number of Fc epsilon RII(+) peripheral blood lymphocytes was observed (Spearman's rank correlation coefficient = 0.79, p less than 0.001 in 27 allergic and Spearman's rank correlation coefficient = 0.72, p less than 0.001 in 19 nonallergic children). In conclusion, serum sFc epsilon RII may be derived mainly from Fc epsilon RII(+) lymphocytes, and may have relationship to the increased production of IgE in early childhood (0-2 y).

Adolescent↗

[Clinical evaluation of clarithromycin in pediatric patients].

A clinical evaluation of clarithromycin (TE-031, A-56268), a newly synthesized macrolide antibiotic, was made for its efficacy and safety in 30 patients with ages ranging from 8 month-old to 12 year- 2 month-old with mycoplasmal and bacterial infections. The obtained results are summarized below. 1. A pharmacokinetic study following oral administration of TE-031 at 10 mg/kg (granule) or 5.5 mg/kg (tablet) resulted in blood concentrations and urinary recovery rates higher than with other macrolides. 2. TE-031 was administered orally to 5 patients with Mycoplasma pneumonia, 21 patients with pneumonia or bronchopneumonia, 2 patients with pertussis and 2 patients with enterocolitis at daily dosages ranging 11.1-31.6 mg/kg divided into 3. Clinical evaluations of these 30 patients were as follows; excellent: 19 patients, good: 11 patients. The efficacy rate was 100%. 3. Neither clinical adverse reaction nor abnormal laboratory data was found in any of these 30 patients. 4. MICs of TE-031 against 10 strains of bacteria isolated from 10 patients with pneumonia or bronchopneumonia were as follows. MICs against 3, 2 and 2 out of 7 strains of Streptococcus pneumoniae were less than 0.025 microgram/ml, 0.05 microgram/ml and 0.10 microgram/ml, respectively. MIC against a strain of Haemophilus influenzae was 3.13 micrograms/ml. MICs of 2 strains of Branhamella catarrhalis were 0.20 microgram/ml. 5. TE-031 is considered to be a new useful and safe antibiotic in pediatric patient with an excellent bactericidal capacity.

Age Factors↗

Interactions of thyroid hormones with L-(3H) glutamate binding sites, with special reference to N-methyl-D-aspartate receptors.

An L-(3H)glutamate binding assay was developed in which 82% of the specific binding is to a site that corresponds to the N-methyl-D-aspartate receptor. The effects of various anticonvulsants and thyroid hormones were investigated with this assay. Anticonvulsants did not affect L-(3H)glutamate binding, while L- and D-isomers of triiodothyronine and thyroxine inhibited L-(3H)glutamate binding significantly. Scatchard analysis showed that thyroid hormones interacted with L-(3H)glutamate binding competitively. The interactions of thyroid hormones with NMDA-sensitive L-(3H)glutamate binding may be one of the mechanisms by which these hormones affect the central nervous system.

Amino Acids↗

Biochemical characterization of U937 cells resistant to L-asparaginase: the role of asparagine synthetase.

A human histiocytic lymphoma cell line, U937, is highly sensitive to L-asparaginase with an ID50 of about 0.0001 U/ml after 72 hr of culture. When U937 cells were made resistant to either L-asparaginase (1 U/ml) or asparagine deprivation, the activity of asparagine synthetase increased to 80- or 7-fold of the wild type, respectively. The phenotype of the resistance to L-asparaginase turned out to be stable under nonselective conditions for over several months. The hybrids between L-asparaginase sensitive (Molt4) and resistant (HL-60) cell lines revealed the latter phenotype in terms of L-asparaginase sensitivity and the activity of asparagine synthetase. Furthermore, U937 cells resistant to L-asparaginase could survive in glutamine-free media with 1.5-fold elevation of glutamine synthetase activity. These results altogether clarify the role of asparagine synthetase in L-asparaginase toxicity and have a good implication for the clinical use of L-asparaginase.

Amino Acids↗

Sotos syndrome with a balanced reciprocal translocation t(2;12)(q33.3;q15).

A balanced reciprocal translocation, 46,XY, t(2;12), was detected in a male infant who had the characteristic features of Sotos syndrome. His father's karyotype was normal, but his mother and an older brother had the same chromosomal abnormality without a history or clinical features of Sotos syndrome.

Chromosome Banding↗

[Clinical evaluation of sulbactam/ampicillin in children].

Sulbactam/Ampicillin (SBT/ABPC), a combination at a fixed ratio of ABPC and SBT which is an irreversible inhibitor of beta-lactamase in a 2:1 ratio, was clinically evaluated for its efficacy and safety in 24 patients with ages from 5 month-old to 12 years old with bacterial infection. The results obtained are summarized as follows. 1. A pharmacokinetic study following 30 mg/kg SBT/ABPC administration by 30 minutes drip infusion or intravenous bolus injection showed that mean half-lives of SBT and ABPC were 48.9 minutes and 40.2 minutes, respectively, and mean urinary excretion rates of SBT and ABPC in the first 6 hours were 67.1% and 48.3%, respectively. 2. SBT/ABPC was administered to 14 patients with bronchopneumonia, 4 patients with tonsillitis, a patient each with acute upper respiratory infection, with submandibular lymphadenitis, with phlegmon, with enterocolitis, with pyelonephritis and with cystitis at a daily dosage of 88.2-133.3 mg/kg, divided into 3 or 4, by intravenous bolus injection or by 30 minutes drip infusion. Clinical responses of the 24 patients were as follows: excellent: 17 patients, good: 7 patients. The efficacy rate was 100%. 3. Neither clinical adverse reactions nor abnormal laboratory test values, except slight eosinophilia in a patient and an elevation of GOT, GPT in another were observed. 4. MICs of SBT/ABPC against 7 strong beta-lactamase producing strains isolated from some of the patients were as follows. MIC against a strain of Staphylococcus aureus was 3.13 micrograms/ml, MICs against 2 out of 5 strains of Branhamella catarrhalis were 0.10 microgram/ml and those of the remaining 3 strains were 0.20 microgram/ml. MIC against a strain of Haemophilus parainfluenzae was 3.13 micrograms/ml. 5. These data described above show that SBT/ABPC has excellent bactericidal capacity against beta-lactamase producing bacteria as well as beta-lactamase non-producing Gram-positive and negative bacteria and suggest that SBT/ABPC is a very useful antibiotic for pediatric patients.

Age Factors↗

[Clinical studies on cefixime in pediatrics].

Clinical usefulness of cefixime (CFIX), a new oral cephalosporin antibiotic, in pediatric field was investigated. The results obtained were summarized as follows. 1. The clinical efficacy of CFIX was investigated in a total of 138 children including 49 with upper respiratory tract infections (RTI), 22 with acute bronchitis, 18 with pneumonia, 19 with scarlet fever and 21 with urinary tract infections (UTI). 2. Clinical effectiveness was excellent in 58, good in 60, fair in 14 and poor in 3, with an overall efficacy rate of 87.4%. The efficacy rate classified according to types of infection were 85.7% in upper RTI, 89.5% in acute bronchitis, 94.4% in pneumonia, 78.9% in scarlet fever, and 90.5% in UTI. 3. Out of the suspected causative organisms, 43 strains of a total of 50 strains isolated were eradicated. The bacteriological eradication rate was 86.0%. (Haemophilus influenzae 100%, Haemophilus parainfluenzae 100%, Streptococcus pyogenes 88.5%, Escherichia coli 85.7%). 4. One hundred forty four children were analyzed for side effect. Side effects were observed in 2 children (1.4%) with diarrhea in 1 and anorexia in another. Abnormal laboratory test results were recorded in 4 children (3.3%). The above results suggest that CFIX is a very useful new oral cephalosporin for the treatment of bacterial infections in children.

Adolescent↗

[Clinical evaluation of cefodizime in children].

Cefodizime (THR-221, CDZM), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 20 children with bacterial infections (Table 1), and the following results were obtained. 1. CDZM was administered in 3 or 4 divided doses at daily dosages ranging from 54.5 to 84.2 mg/kg administered by 30 minutes drip infusion or intravenous injection to 20 patients (7 cases of acute tonsillitis, 6 cases of pneumonia, 2 cases each of bronchitis and suppurative cervical lymphadenitis, and 1 case each of acute pharyngitis, acute enteritis and furunculosis) and the following clinical results were obtained: excellent, 7 cases; good, 11 cases; fair, 2 cases. The overall efficacy rate was 90% (Table 4). 2. MICs of CDZM against 15 strains of isolated organisms are shown in Table 2. MICs against all 7 strains of Haemophilus influenzae were less than 0.025 micrograms/ml. MIC against 1 out of 5 strains of Streptococcus pneumoniae was 0.05 micrograms/ml and those against 2 strains were 0.10 micrograms/ml and against the other 2 were 0.20 micrograms/ml. MICs against 3 strains of Staphylococcus aureus were 1.56, 25 and higher than 100 micrograms/ml, respectively. 3. No clinical adverse reaction was observed in any of the 20 patients. Eosinophilia was observed in 2 cases. A slight elevation of S-GOT was found in 1 patient (case No. 8) and moderate elevation of S-GOT and S-GPT in another (case No. 18) (Table 4). In case No. 18, the S-GOT and S-GPT activity improved after the administration of the drug was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Allogeneic bone marrow transplantation in a case of acute lymphoblastic leukemia with positive Philadelphia chromosome].

A 12-year-old boy with Philadelphia chromosome positive acute lymphoblastic leukemia received bone marrow transplantation (BMT) from an HLA identical sibling during the second remission. The diagnosis was made at the age of nine. Laboratory examination on admission revealed remarkable leukocytosis (92,000/microliters) with 93% lymphoblasts in the peripheral blood. Blastic cells were FAB L1 common ALL. Chromosomal study on both peripheral blood and bone marrow cells showed that lymphoblasts had an abnormal karyotype of 47, XY, inv (9), t(9; 22), +17. One month later he achieved remission by induction therapy consisting of vincristine, L-asparaginase, doxorubicin, and prednisolone. He was given intrathecal injection of methotrexate and cranial irradiation of 24 Gy for CNS prophylaxis. The cells with Philadelphia chromosome disappeared during remission. Hematological relapse occurred twenty one months later after first remission on April, 1986. He received re-induction therapy including L-Asp VDP, and high-doses of cyclophosphamide, methotrexate and araC. He obtained karyotypic remission on October 1986. Subsequently, bone marrow transplantation was performed following high-dose araC, CY and TBI as preconditioning on December 18, 1986. Methotrexate and cyclosporin A were given intravenously to prevent GVHD. On day 14, karyotypic conversion was detected, suggesting the successful bone marrow grafting. Acute GVHD appeared on day 25, and was treated with prednisolone and cyclosporin A. Prednisolone was tapered by day 80. On day 91, cyclosporin A was discontinued because herpes zoster occurred. Acyclovir was effective, but skin GVHD reappeared. With low-dose prednisolone, skin GVHD improved. Sicca syndrome soon appeared and was followed by chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Computed tomographic study of children with microcephaly].

Computed tomographic (CT) brain scanning was performed on fifty-eight infants and children with microcephaly. CT scans were useful for detecting unsuspected brain lesions and for diagnosing underlying diseases. The head size did not correlate with the CT findings, the degree of mental retardation, or the existence of motor disturbance or epilepsy. On the other hand, the CT findings were correlated with the degree of mental retardation, and the existence of motor disturbance or epilepsy. CT scans were useful for determining the prognosis of the microcephaly.

Brain↗