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Y Niida

Publications and source records attributed to Y Niida.

32 records · Page 2Linked to original sources

Urinary excretion of mefenamic acid and its metabolites including their esterglucuronides in preterm infants undergoing mefenamic acid therapy.

Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.

Anti-Inflammatory Agents, Non-Steroidal↗

[A psychological burden on patients with clinical trials during anesthesia].

We investigated with questionnaires, psychological outline of 30 patients, who were requested to participate in clinical trials of anti-tachycardia drugs during anesthesia. Although 14 patients consented to the trial, the consent was not based on adequate understanding or volunteerism in 3 patients. Nine patients of the consented group were anxious about the possible use of the trial drug. Eight patients of the rejected group felt anxiety on surgery and anesthesia, which was the most common reason for rejection. Forty % of refused patients felt a guilty conscience or embarrassed. Although we tried to obtain patients' consent following governmental and institutional regulations and guidelines, not only the consented but also the refused patients suffer from psychological burden with the clinical trial. It is of concern that recruitment to the trial enhances anxiety of the patients as they already feel uneasiness, unrest, and insecurity facing anesthesia and surgery. To avoid entry of less informed or unwilling patients to the clinical trial, we must secure patients' veto, and recruitment should be performed by clinicians who are not involved in anesthesia practice.

Anesthesia↗

Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan.

Deficiencies of Bruton's tyrosine kinase (Btk) have been implicated in the pathogenesis of human X-linked agammaglobulinemia (XLA). The distinctive phenotype observed in B-cell deficiency indicates the crucial role of Btk in B-cell development. This report describes a nationwide study of Btk deficiency in Japan, covering 51 XLA patients (35 independent families). Along with the identification of mutations, the resulting protein products were characterized by an in vitro kinase assay and a Western blot analysis. Thirty-one of the families were found to have mutations in the coding region of Btk. Although mutations were not found in the cDNA of 4 families, the Btk transcripts of these patients were greatly reduced. The identification of several novel missense mutations, in combination with the result of other studies, clarified the presence of two (missense) mutation hot spots, one in the SH1 and the other in the PH domain. The absence of kinase activity seen in 32 of the families underscored the importance of Btk protein analysis as a diagnostic indicator of XLA. The protein analysis also clarified the different effects of missense mutations on kinase activity and protein stability.

Adolescent↗

Expression of L-selectin (CD62L) discriminates Th1- and Th2-like cytokine-producing memory CD4+ T cells.

Human memory (CD45RO+) CD4+ T cells can be distinguished into two subpopulations on the basis of expression of the lymph node homing receptor, L-selectin (CD62L). In a prior study we showed that human L-selectin-positive memory T-helper (Th) cells promote the maturation of IgG- and IgA-producing cells by naive B cells. To further elucidate the contribution of memory CD4+ T cells to B-cell differentiation, human memory CD4+ T cells with or without L-selectin expression were evaluated for production of cytokines that participate in regulation of immunoglobulin production. It was found that L-selectin-positive human memory CD4+ T cells produce mainly interleukin (IL)-4 and IL-5, whereas L-selectin-negative CD4+ T cells produce mainly interferon-gamma (IFN-gamma). This profile of cytokine expression coincides with the profile that distinguishes Th1 and Th2 subsets. In contrast to the murine system, IL-10 production was similarly contributed by human L-selectin-positive and -negative memory CD4+ T-cell subpopulations. These results suggest that the human L-selectin-negative and -positive subpopulations of human memory CD4+ T cells contain Th1-like and Th2-like cytokine-producing cells, respectively.

Adult↗

An acrosomal protein, sp32, in mammalian sperm is a binding protein specific for two proacrosins and an acrosin intermediate.

An acrosomal protein, sp32, was completely purified from acid extracts of ejaculated porcine sperm. Purified sp32 gave a single 32-kDa protein band on SDS-polyacrylamide gel electrophoresis and was characterized as a binding protein specific for 55-, 53-, and 49-kDa forms of (pro)acrosin. This protein was not capable of binding a 43-kDa acrosin intermediate and 35-kDa mature acrosin. sp32 significantly accelerated autoactivation of proacrosin at a basic pH in vitro and affected the maturation pathway of proacrosin. In the presence of sp32, the 49-kDa acrosin intermediate from the 55- and 53-kDa proacrosins was accumulated, instead of the 43-kDa acrosin intermediate. These results suggest that sp32 interacts with both the amino- and carboxyl-terminal sequences of the 53-kDa proacrosin. The cDNA clones coding for porcine and guinea pig sp32 have been identified from testis cDNA libraries in lambda gt11. The deduced amino acid sequence indicates that sp32 is initially synthesized as a 61-kDa precursor protein with a putative signal peptide at the amino terminus. The carboxyl-terminal half of the precursor molecule corresponds to the mature sp32. Thus, sp32 is produced by post-translational modification of the precursor. The binding of sp32 to proacrosin may be involved in packaging the acrosin zymogen into the acrosomal matrix.

Acrosin↗

Mature helper T cell requirement for immunoglobulin production by neonatal native B cells injected intraperitoneally into severe combined immunodeficient (SCID) mice.

It is accepted that human neonatal naive B cells produce mainly IgM in vivo as well as in vitro. Our previous work has demonstrated that i.p. injection of neonatal B cells together with adult mature T cells induces substantial levels of human IgG in the serum of SCID recipient mice. The present study was further attempted to determine the cellular components required for immunoglobulin production by neonatal B cells in SCID mice. When neonatal B and adult T cells were transferred into the SCID mice, human immunoglobulins, largely of IgG, were maximally detected in the serum around 6 weeks after a cell transfer. Depletion of CD4+ T cells from adult T cells resulted in undetectable levels of human immunoglobulin in the serum. By contrast, CD4+ T cell-enriched populations exhibited an enhancing effect on immunoglobulin production by neonatal B cells. Higher levels of immunoglobulin, including IgA and IgM, were detected in the peritoneal fluid than in the serum as early as 2 weeks after the cell transfer. Human T cells expressing activation antigens such as CD45RO and HLA-DR antigens were identified in the peritoneal lavages. These results suggest that neonatal naive B cells are able to differentiate into cells producing all classes of immunoglobulin in the presence of mature CD4+ T cells in a SCID mouse environment. The peritoneal cavity of SCID mice appears to provide a suitable place for immune responses by human cells, possibly in association with a certain xenogeneic reaction.

Adult↗

Pharmacokinetics of mefenamic acid in preterm infants with patent ductus arteriosus.

The pharmacokinetics of mefenamic acid (MA), 2 mg/kg, were studied in 17 preterm infants with symptomatic patent ductus arteriosus. They were given this dosage orally at 24 h intervals. There were marked inter-individual differences in some of the pharmacokinetic parameters after the first dose; peak plasma concentration (Cmax) varied from 1.2 to 6.1 micrograms/mL with a mean of 3.8 micrograms/mL, time to reach Cmax (tmax) varied from 2 to 18 h with a mean of 7.7 h and plasma half-life (t1/2) varied from 3.8 to 43.6 h with a mean of 18.7 h. The group of infants (10/17) who had ductus closure after the first dose had significantly lower clearance (P < 0.01), longer t1/2 (P < 0.01) and higher 24 h plasma concentration (P < 0.001) compared to the group of infants (7/17) who had no ductus closure after the first dose. It appeared that the plasma concentration of MA had to be above 2.0 micrograms/mL and maintained at this concentration for at least 12 h for MA associated with ductus closure in preterm infants to take effect. In view of the inter-individual variation of plasma MA concentration and the effective plasma concentration, we suggest that measurement of the plasma concentration should be done 24 h after the first dose. This might be useful for safe and effective therapy for infants with ductus closure failure after the first dose.

Administration, Oral↗

Resetting of regional preload due to ventricular shape change alters diastolic and systolic performance.

The diastolic and systolic pressure of one ventricle is increased by an increase in volume and/or pressure of the opposite ventricle; however, a mechanism for the ventricular interaction remains unclear. We hypothesized that the shape change of one ventricle elicited by the opposite ventricle would lead to resetting of the regional length, which may explain the ventricular interaction. We used 15 cross-circulated isovolumically contracting canine hearts in which both ventricular volumes were independently controlled. Diastolic regional segment area was calculated by multiplying circumferential and longitudinal lengths on right ventricular free wall (RVFW; n = 6), interventricular septum (IVS; n = 11), and left ventricular (LV) FW (n = 12). The regional area at relatively small volumes of both ventricles were expressed as 100%. With constant RV volume, increasing LV from 7 to 19 ml increased RV diastolic and systolic pressures by 2.7 and 5.5 mmHg, respectively. Conversely, increasing RV volume increased LV diastolic and systolic pressures by 2.3 and 7.5 mmHg, respectively. Increasing LV volume increased RVFW regional area from 121.0 to 124.6% (P < 0.01) and increased IVS regional area from 103.3 to 108.7% (P < 0.01), whereas the RV volume was held constant. Increasing RV volume also increased LVFW and IVS regional areas from 109.9 to 111.6% (P < 0.01) and from 106.8 to 108.9% (P < 0.05), respectively. Ventricular shape change elicited by ventricular interaction will increase the regional wall area, even though the volume of the chamber is unchanged. The increase in the regional area alters the position of the tissue on its resting and active length-tension relations and, thus, leads to enhancement of the chamber pressure.

Animals↗

Evaluation of diagnostic assays for neonatal and infantile chlamydial infections.

Several diagnostic assays for neonatal and infantile chlamydial infections, isolation with tissue culture, antigen detection by enzyme immunoassay (EIA) (IDEIA Chlamydia test), a nonisotopic DNA probe (Gen-Probe PACE 2 assay), serum IgM antibody detection by EIA (SeroELISA Chlamydia TRUE IgM), and polymerase chain reaction (PCR), were evaluated. Of 210 clinical specimens (170 nasopharyngeal and 40 conjunctival swabs) from 53 neonates and 102 infants with respiratory insufficiency and respiratory tract infections which were suspected to be associated chlamydial infection, chlamydial antigens were detected in 30 by IDEIA Chlamydia. Of these 30 samples, C. trachomatis was isolated from 27 specimens. Samples from 15 neonates and 6 infants were culture-positive and IDEIA Chlamydia-positive. Of 30 samples, 27 were tested with PCR and 8 with DNA probe. Twenty-three of 27 specimens were positive with PCR, while only one specimen was positive with DNA probe. EIA can be used for the diagnosis and screening of neonatal and infantile chlamydial infections.

Antibodies, Bacterial↗

[Evaluation of chlamydial IgM antibodies for clinical diagnosis].

Chlamydia trachomatis (C. trachomatis), C. psittaci, and C. pneumoniae are now well established as pathogens of respiratory infections including pneumonia. Serum samples from 223 infants and children with pneumonia, 31 patients with adult inclusion conjunctivitis, 16 parents of babies with neonatal inclusion conjunctivitis and others were tested for IgM antibodies to Chlamydiae. Diagnostic kits for chlamydial IgM antibodies (SeroELISA and IPAzyme) have been also evaluated for their diagnostic value. It was found that detection of specific IgM antibodies with SeroELISA has a diagnostic value in chlamydial pneumonias.

Adolescent↗

Remarkable changes in the plasma levels of pituitary protein "7B2" during childhood.

We measured plasma immunoreactive (IR)-7B2 concentrations in 96 children (57 males and 39 females) from the newborn period to 20 yr of age. Plasma IR-7B2 concentrations in infants less than 2 yr of age (range 175-580 pg/ml, n = 19) were much higher than those in adults (range 20-138 pg/ml). Plasma levels of IR-7B2 decreased with age during childhood to reach the adult level at 15-20 yr. Significant negative correlations were found between plasma levels of IR-7B2 and dehydroepiandrosterone sulfate (r = -0.4154, p less than 0.05, n = 27), luteinizing hormone (r = -0.4948, p less than 0.05, n = 20) and follicle-stimulating hormone (r = -0.4682, p less than 0.05, n = 20). The possibility of a relationship between the reduction of plasma IR-7B2 levels and pubertal development warrants attention.

Adolescent↗

Lactoferrin in middle ear effusion.

Lactoferrin (LF) level in the middle ear effusion of patients with otitis media with effusion (OME) was determined by using an Enzyme-linked immunosorbent assay (ELISA) to find the information on non-specific immunity in the middle ear cavity. Lactate dehydrogenase (LDH), an intracellular enzyme, was also measured by spectrophotometer. We investigated cytological findings of middle ear effusion and classified cellular findings into five classes; Neutrophil dominant type, Lymphocytic-monocytic type, Mixed type, Cellular remnants type, and Too few cells type. LF and LDH levels in average: Serum, LF 1.14 microgram/ml, LDH 330.4 IU/l; Few cells type, LF 45.25 micrograms/ml, LDH 2,727.5 IU/l; Lymphocytic-monocytic type, LF 107.11 micrograms/ml, LDH 10,197.8 IU/l; Neutrophil dominant type, LF 99.73 micrograms/ml, LDH 10,580 IU/l; Mixed type, LF 163.71 micrograms/ml, LDH 19,342.9 IU/l; Cellular remnants type, LF 127.6 micrograms/ml, LDH 9,122 IU/l. LF level is high when cellular factors are rich in middle ear effusion.

Child↗