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Biomedical subjects

A Matsui

Publications and source records attributed to A Matsui.

At least 37 records · Page 2Linked to original sources
PubMed2001

Haplotypes of the 5' region of the IL-4 gene and SNPs in the intergene sequence between the IL-4 and IL-13 genes are associated with atopic asthma.

IL-4 and IL-13 are important in IgE synthesis and allergic inflammation. Therefore, genes encoding IL-4 and IL-13 are candidates for predisposition to asthma and atopy. A recent study in the YAC transgenic mouse has revealed that one of the conserved noncoding sequences (CNS-1) between IL-4 and IL-13 influences the expression of IL-4, IL-5, and IL-13, suggesting that CNS-1 acts as a coordinate regulator of these genes. This investigation screened for mutations in the 13-kb region between IL-4 and IL-13, which includes the human equivalent of the murine CNS-1. Four single nucleotide polymorphisms (SNPs) were found in the region between IL-4 and IL-13 (IL-4-IL-13SNP1, IL-4-IL-13SNP2, IL-4-IL-13SNP3, and IL-4-IL-13SNP4). There was no mutation in the human CNS-1. We genotyped these and other previously reported polymorphisms in IL-4 and IL-13 using asthmatic families, and examined association by transmission disequilibrium test. Two-locus haplotype analysis revealed that haplotypes composed of the IL-4 RP2del, IL-4 +33T, or IL-4 -589T alleles and either IL-4-IL-13SNP3G or IL-4-IL-13SNP4C are transmitted significantly to asthma-affected children (p = 0.002). This data suggests that haplotypes composed of the 5' region polymorphisms in the IL-4 gene and SNPs in the intergene sequence between IL-4 and IL-13 influence the development of asthma.

Adolescent↗
PubMed2001

TT virus infection in cases of fulminant hepatic failure-evaluation by clonality based on amino acid sequence of hypervariable regions.

The significance of TT virus (TTV) infection in the pathogenesis of acute liver disease is uncertain. Serum TTV-DNA was determined by polymarase-chain reaction (PCR) methods using both hemi-nested (NG059/NG063 and NG061/NG063) and single-step (T801/T935) primers in four patients with fulminant hepatic failure and one patient with late onset hepatic failure in whom hepatitis A virus (HAV) and hepatitis B virus (HBV) markers were negative. Of these five patients, the TTV-DNA was positive in two patients with fulminant hepatic failure by both PCRs before receiving blood transfusion and/or blood-products infusion. Therapies including plasma exchange with blood hemodiafiltration was performed in both patients, and one survived. The non-survivor was an 18-year-old woman with TTV genotype 2 infection. In this patient, the TTV-DNA by PCRs with both primers was positive transiently when serum ALT levels were elevated. The survivor was a 78-year-old woman with infections of TTV genotype 1b and hepatitis C virus (HCV), in whom serum ALT levels returned to normal at 3 weeks after the start of the therapies, but fluctuated after 10 weeks. TTV-DNA measured by hemi-nested primers and HCV-RNA were negative when serum ALT levels decreased, but became positive later. Semi-quantitative PCR using single-step primers revealed that serum TTV-DNA levels changed in correlation with both serum ALT and HCV-RNA levels. Amino acid sequences of hypervariable regions were identical in six out of nine clones isolated from the sera before the therapies and sequence divergence was minimal even in the other three clones, suggesting that TTV proliferated with clonality in the process of fulminant hepatic failure. We conclude that clonally proliferating TTV may contribute to fulminant hepatic failure as a solitary infectious agent or a co-infectious agent with HCV.

Journal Article↗
PubMed2001

Identification of missense mutation in the IL12B gene: lack of association between IL12B polymorphisms and asthma and allergic rhinitis in the Japanese population.

Interleukin-12 (IL-12) is a macrophage-derived cytokine that modulates T lymphocyte responses and can suppress allergic inflammation. In a genome-wide screen, we found strong evidence for linkage of atopic asthma with marker D5S1352, located close to IL12B, with a maximum lod score of 4.34. We screened for mutation in IL12B and found three novel (-4475-4insG, Glu186Asp and Ser226Asn) variants and one previously reported (1188A>C) variant in IL12B, and conducted transmission disequilibrium tests in families identified through children with atopic asthma or allergic rhinitis. Frequencies of the Asn226 and 1188C alleles in the parents were 0.04 and 0.5, respectively. Preferential transmission of either the Ser226/Asn226 or 1188A/C allele to asthma-affected or rhinitis-affected children was not observed (P > 0.1) and was not associated significantly with total serum IgE level (P > 0.1). Our results indicate that polymorphisms in IL12B are not likely to be associated with the development of atopy-related phenotypes.

Adolescent↗
PubMed2001

Association between a new polymorphism in the activation-induced cytidine deaminase gene and atopic asthma and the regulation of total serum IgE levels.

BACKGROUND: Activation-induced cytidine deaminase (AICDA) is a recently identified RNA-editing deaminase that plays an important role in class-switching. Defects in AICDA result in a hyper-IgM phenotype and lack of IgG, IgA, and IgE in both human beings and mice. OBJECTIVE: The aim of this study was to determine whether the AICDA gene is related to regulation of total serum IgE and development of atopic asthma. METHODS: We screened for polymorphisms in the 5;-flanking and coding regions of the AICDA gene in subjects with atopic asthma and analyzed the effect of these polymorphisms on the development of atopic asthma and on total serum IgE levels in Japanese asthmatic families. RESULTS: We identified 3 novel polymorphisms (5923A/G, 7888C/T, and 8578A/C) and 1 rare variant (Arg25Cys) in the AICDA gene. Transmission disequilibrium testing showed that the 7888C allele was transmitted preferentially to asthma-affected children (P =.007). Mean log [total serum IgE] levels of parents with the 7888C/7888C, 7888C/7888T, and 7888T/7888T genotypes were 2.12, 1.99, and 1.77, respectively, and a significant association was observed between the genotypes (P =.02). In RT-PCR experiments, we found 2 novel splice variants of AICDA, one lacking all of exon 4 (variant 1; 367 base pairs) and the other lacking the first 30 base pairs of exon 4 (variant 2; 453 base pairs). These variants were not associated with the 7888C/T polymorphism. CONCLUSION: The 7888C/T polymorphism might be associated with the pathogenesis of atopic asthma and the regulation of total serum IgE levels.

APOBEC-1 Deaminase↗
PubMed2001

Signal-averaged electrocardiogram in children and adolescents with insulin-dependent diabetes mellitus.

UNLABELLED: We report on the potential usefulness of the signal-averaged electrocardiogram (SA-ECG) in young patients with insulin-dependent diabetes mellitus (IDDM) to predict subclinical cardiovascular complications. Sixteen patients with IDDM and 18 age-matched healthy subjects were studied. The IDDM group included 4 males and 12 females, aged 7 to 20 y (mean 14.2 +/- 3.8 y, +/- SD). The duration from the onset of IDDM to the study ranged from 1.2 to 9.8 y (mean 5.4 +/- 3.8 y), and HbAlc value ranged from 6.6 to 12.4% (mean, 10.0 +/- 1.8%). SA-ECG was recorded and analyzed using the methods described by Simson. Values of filtered QRS duration (f-QRS), root mean square voltage (RMS), the duration of low amplitude signal (LAS) and late duration (LD) were calculated and compared between the groups. These parameters were not significantly different between the IDDM and control groups. However, in patients with poor glycemic control (HbAlc >10%), f-QRS was long and RMS was significantly low (p < 0.05, each) compared with the control group. Three patients with IDDM were positive for ventricular late potentials, although none had ventricular tachyarrhythmia. None of the control subjects showed ventricular late potentials. CONCLUSION: Certain parameters of SA-ECG showed abnormal values in IDDM patients with poor glycemic control. Thus, SA-ECG is a potentially useful and non-invasive method for the assessment of subclinical cardiac impairment in diabetic children and adolescents.

Adolescent↗
PubMed2001

Membrane fusion between liposomes composed of acidic phospholipids and neutral phospholipids induced by melittin: a differential scanning calorimetric study.

Melittin-induced membrane fusion between neutral and acidic phospholipids was examined in liposome systems with a high-sensitivity differential scanning calorimeter. Membrane fusion could be detected by calorimetric measurement by observing thermograms of mixed liposomal lipids. The roles of hydrophobic and electrostatic interactions were investigated in membrane fusion induced by melittin. Melittin, a bee venom peptide, is composed of a hydrophobic region including hydrophobic amino acids and a positively charged region including basic amino acids. When phosphatidylcholine liposomes were prepared in the presence of melittin, reductions in the phase transition enthalpies were observed in the following order; dimyristoylphosphatidylcholine (DMPC) > dipalmitoylphosphatidylcholine (DPPC) > distearoylphosphatidylcholine (DSPC) > dielaidoylphosphatidylcholine (DEPC). The plase transition enthalpy of an acidic phospholipid, dipalmitoylphosphatidylserine (DPPS), was raised by melittin at low concentrations, then reduced at higher concentrations. DPPC liposomes prepared in melittin solution were fused with DPPS liposomes when the liposomal dispersions were mixed and incubated. Similar fusion was observed between dipalmitoylphosphatidylcholine and dimyristoylphosphatidic acid (DMPA) liposomes. These results indicate that a peptide including hydrophobic and basic regions can mediate membrane fusion between neutral and acidic liposomes by hydrophobic and electrostatic interactions.

Calorimetry, Differential Scanning↗
PubMed2001

Detection of cardiac hypertrophy in the fetus by approximation of the current dipole using magnetocardiography.

To determine the developmental changes in the myocardial current during fetal life, and to evaluate the clinical usefulness of magnetocardiography for prenatal diagnosis of cardiac hypertrophy or enlargement, we approximated the magnitude of the one-current dipole of the fetal heart using fetal magnetocardiography (fMCG). A total of 95 fetuses with gestational age of 20-40 wk were included in this study. fMCG was recorded with a nine-channel superconducting quantum interference device system in a magnetically shielded room. The magnitude of the dipole (Q) was calculated using an equation based on the fMCG amplitude obtained on the maternal abdomen and the distance between the maternal surface and fetal heart measured ultrasonographically. In uncomplicated pregnancies, the Q value correlated significantly with gestational age, reflecting an increase in the amount of myocardial current, i.e. myocardial mass. Moreover, the Q values in fetuses with cardiomegaly caused by various cardiovascular abnormalities tended to be higher than the normal values. Although there are some limitations of the methodology based on the half-space model, and fetal orientation may influence the magnitude of the dipole, making it smaller, fMCG recorded with a multichannel superconducting quantum interference device system is a clinically useful tool for noninvasive, prenatal, and electrical evaluation of fetal cardiac hypertrophy.

Cardiomegaly↗
PubMed2001

[Regional variation in bone mineral density and motor function in children with cerebral palsy].

Bone mineral density (BMD) and motor activity of the upper extremities, were studied in 18 children with spastic cerebral palsy (CP group) and 12 age-matched normal boys (control group). The motor activity was monitored by a piezoelectric transducer. Whole body BMD as well as BMD of the head, upper limbs, ribs, spine, pelvis, and lower limbs was evaluated by dual energy x-ray absorptiometry. In the CP group, BMDs were lower compared to control group in the whole body and in all the body regions (except for the head) especially in the pelvis and lower limbs. BMDs of these regions were higher in walking patients than in bed-ridden, rolling, and crawling patients. Motor activities in the upper extremities were lower in the CP than in the control group. BMD increased with developing motor activity in the upper extremities. These results implicate diminished BMDs of the lower limbs and pelvis, which are associated with standing and walking, to the high incidence of femur fractures in CP.

Absorptiometry, Photon↗
PubMed2001

C-reactive protein frequently localizes in the kidney in glomerular diseases.

AIM: In recent reports, C-reactive protein (CRP) has emerged as a component that may play important roles in atherogenesis. Based on the analogies set out in a previous report between focal-segmental sclerosis and atherosclerosis, we hypothesized that CRP contributes to the pathogenesis of glomerular diseases. To our knowledge, no immunohistochemical study of CRP localization in the kidneys has been previously reported. PATIENTS AND METHODS: In the present study, we investigated 106 kidney biopsy specimens from children with various types of glomerular diseases and minor glomerular abnormalities. Of the 106 cases, 74 were proliferative diseases, 17 were non-proliferative diseases, and 15 were minimal-change nephrotic syndrome (MCNS). Immunohistochemical staining was performed using monoclonal antibody to CRP. RESULTS: CRP immunoreactivity was found in 48 of 106 (45.3%) specimens. CRP deposition was encountered more often in patients with proliferative diseases (56.8%) than in those with non-proliferative diseases (23.5%) (p < 0.01). CRP deposition, most frequently observed along the capillary walls of glomeruli, was found in 33 of 46 (71.7%) cases with positive expression of CRP. CRP was also located in the peritubular capillary walls and small vessels in the interstitium in 13 of 46 cases (28.3%). CRP deposition was also found in 2 of 15 cases of MCNS. The two MCNS specimens showing positive CRP immunoreactivity were both from patients who had undergone cyclosporin therapy. CRP deposition was not shown in any cases treated with steroids or cyclophosphamide. The cases of patients who had undergone renal biopsies within 6 months after onset revealed a tendency toward positive CRP deposition. The clinical outcomes at the latest follow-up were quite similar between the groups of patients with and without CRP deposition. CONCLUSIONS: We surmise that circulating CRP may deposit at the site of endothelial injury, and may not be relevant to the progression of renal lesions.

Adolescent↗
PubMed2001

[Current status of adjuvant endocrine therapy for hormone responsive breast cancer].

Three important meetings on adjuvant hormone therapy for breast cancer were held recently: the 5th EBCTCG Meeting, NIH Consensus Meeting, 7th International Conference on Adjuvant Therapy of Primary Breast Cancer. The conclusions of these meetings are: 1. adjuvant hormone therapy should be indicated only for patients with estrogen/progesterone receptor positive cancer, 2. five years of tamoxifen is the standard care at present, 3. ovarian ablation by any means has been proved effective in premenopausal patients and LH-RH agonist should be given at least two years, and 4. aromatase inhibitors should not be used in clinical practice, because several prospective randomized trials are ongoing at present. The patients treated with LH-RH agonist combined with tamoxifen showed better relapse-free survival compared with LH-RH agonist alone in the INT-0101 trial. This was an important trial because combined hormone therapy had not been proven more effective than individual hormone therapy previously. Combined hormone therapy including LH-RH agonist may be considered in premenopausal patients. There is a growing consensus that chemotherapy is effective through the ovarian suppression. In this sense, hormonal therapy should be considered first for hormone responsive patients. On the contrary, standard chemotherapy has shifted from CMF combination to an anthracycline containing regimen. Chemoendocrine therapy may be considered in high risk patients.

Antineoplastic Agents, Hormonal↗
PubMed2001

Delayed onset of systemic lupus erythematosus in a child with endothelial tubuloreticular inclusion.

We report here on an 11-year-old Japanese girl who was found to have proteinuria by routine mass screening urinalysis for school children, and who developed systemic lupus erythematosus (SLE) 21 months later. The initial renal biopsy, performed 3 months after the first visit to Tokyo Medical University Kasumigaura Hospital (TMUKH), revealed membranous glomerulonephritis. In an immunofluorescent study, IgG was the only positive immunoglobulin found. A "full-house" immunofluorescence glomerulopathy, well known as a predictive finding for lupus nephritis, was not detected. Endothelial tubuloreticular inclusions (ETI) were found by electron microscopy. Because the diagnosis of SLE was not established clinically and serologically, the patient was followed every 3 months without drugs. Her urinary findings returned to normal within 18 months. Three months after the last visit, she was sent to Tsukuba University Hospital (TUH) for fever, arthralgia, dyspnea and butterfly rash. She was diagnosed as having SLE, pleuritis, and pericarditis. Although she was treated with methylpredonisolone and oral prednisolone, she developed cardiac tamponade on the 12th day of admission during the course of pneumococcal septicemia. Finally, she was treated successfully with surgical procedures, antibiotics and oral prednisolone and was discharged. We conclude that ETI is a more significant early sign of SLE than "full-house" immmunofluorescence glomerulopathy, especially in pediatric cases.

Cardiac Tamponade↗
PubMed2001

[Clinical experience of intra-arterial chemotherapy for liver metastases of breast cancer patients].

The aim of this study was to evaluate retrospectively the effect of intra-arterial chemotherapy for liver metastases of breast cancer patients. Eleven patients treated between August 1991 and July 1997 at Keio University Hospital, Tokyo, Japan, were the subjects for this study. The duration of disease-free periods after the operation ranged from 9 to 78 months (median 27 months). The site of the recurrence was the liver alone in 6 cases, and the liver and lung in 1 case, bone in 1 case, lymph nodes in 2 cases, and a local region, in 1 case. The main drugs were adriamycin (ADM) and 5-fluorouracil (5-FU), administered in a single injection or continuously via an indwelling catheter in the hepatic artery. This method had a 36% response rate, including PR in 4 cases, NC in 3 cases and PD in 4 cases. The survival duration was 1 to 19 months (median 14 months) following this treatment, and 3 to 49 months (median 17 months) after the recognition of the recurrence. The only side effects of Grade 3 or 4 were leucocytopenia or granulocytopenia and nausea. These results suggest that intra-arterial chemotherapy for liver metastases of breast cancer patients may be an effective method for the control of liver metastases with minor side effects. However, further study may be necessary to establish methods to manage the indwelling catheter and to control patients with multiple metastases of the other organs, to improve the prognosis for recurrent breast cancer patients.

Adult↗
PubMed2000

Lysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells: association with rho-kinase.

We studied the effect of lysophosphatidic acid (LPA) on collagen gel contraction by cultured rat hepatic stellate cells (HSCs) in association with the function of Rho-kinase, one of the target molecules of small GTPase Rho. Binding studies showed a single class-binding site of LPA on HSCs. LPA enhanced the contraction of a collagen lattice seeded with HSCs. LPA increased the number of HSCs with polygonal morphology that contained actin stress fibers, and enhanced the phosphorylation of myosin light chain and the assembly of focal adhesion kinase and RhoA around fibronectin-coated beads seeded on HSCs. The electric cell-substrate impedance sensor system showed that LPA enhanced adhesion of HSC to extracellular substrate. All the effects of LPA were suppressed by Y-27632, Rho-kinase inhibitor. These data support the notion that LPA is involved in modulating HSC morphology, its attachment to surrounding extracellular matrix and its contraction by a mechanism involving Rho-kinase.

Actins↗
PubMed2000

An improved procedure for the development of human mast cells from dispersed fetal liver cells in serum-free culture medium.

The in vitro development of human mast cells from fetal liver cells with recombinant human stem cell factor in serum-containing RPMI was compared to that in AIM-V media with and without serum. Compared to serum-containing media, AIM-V medium caused mast cells to develop earlier and in greater numbers. By 2 weeks, about 60% of cells in serum-free AIM-V medium were phenotypic mast cells, approximately 2 times the percentages in serum-containing media. By 6 weeks the percentages of mast cells were > or =80% under all conditions, but the number of mast cells was 3-4-fold greater in serum-free AIM-V medium than in serum-supplemented media. Mast cells obtained in serum-free AIM-V medium exhibited rounded nuclei, like tissue-derived mast cells; mast cells obtained in serum-supplemented media had segmented nuclei. By 10-12 weeks of culture about 40% of the AIM-V-derived cells showed strong chymase immunocytochemical staining, a pattern observed for only 14% of the cells in serum-containing media. AIM-V medium is a suitable medium for the development of human mast cells in vitro, and permits an earlier, more selective and greater expansion of mast cells than serum-containing media.

Cell Count↗
PubMed2000

Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families.

Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, we conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MLS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups.

Adolescent↗
PubMed2000

Inhibition of intracellular cathepsin activities and suppression of immune responses mediated by helper T lymphocyte type-2 by peroral or intraperitoneal administration of vitamin B6.

We reported that pyridoxal phosphate (PAP), a coenzyme form of vitamin B6, strongly inhibits activities of cathepsin B and weakly inhibits those of cathepsins S, K, and C in vitro. Either intraperitoneal injection or peroral administration of medication doses of vitamin B6 in the diet caused dose-dependent inhibition of hepatic cathepsins B, L, S, and C, and the inhibition was exhibited much more significantly in the case of a high protein diet than in a low protein diet. Administration of vitamin B6 induced the suppression of immune responses against ovalbumin (OVA) mediated by helper T lymphocyte type-2, based on the suppression of antigen processing by cathepsin B inhibition, as in the case of CA-074 administration, a cathepsin B specific inhibitor. Ovalbumin-dependent production of immunoglobulins IgE, IgG1 and interleukin IL-4 was suppressed by administration of medication doses of pyridoxal (PA) or pyridoxine (PI), while the production of IgG2alpha and interferon (INF)-gamma mediated by helper T lymphocyte type 1 was not changed. Administration of medication doses of vitamin B6 caused the inhibition of intracellular cathepsin B activity due to suppression of the functions of helper T lymphocyte type-2.

Administration, Oral↗