Biomedical subjects

I Matsuda

Publications and source records attributed to I Matsuda.

At least 91 records · Page 5Linked to original sources

PubMed1997

Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children.

Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent coronary artery disease (CAD), it may be useful to understand risk factors during childhood and adolescence. In the present study, we evaluated low density lipoprotein particle size (LDL-size) by 2-16% gradient gel electrophoresis in 70 healthy children (30 boys and 40 girls) along with conventional lipid and lipoprotein parameters which are thought to affect LDL-size. The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined. As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and apoA-I were closely associated with LDL-sizes in both sexes (boys: r = -0.694, 0.708 and 0.701, girls: r = -0.579, 0.551 and 0.539, P < 0.001). However, a closer association was found between FER in HDL (FER(HDL)) and LDL-size (boys: r= -0.874, girls: r= -0.642, P < 0.001). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 76% and 41% of the variability in LDL-size in boys and girls, respectively. MER in HDL accounted for additional 4% and 19% in boys and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I had no significant additional effects. Thus, the determination of FER(HDL) is useful to predict the particle size of LDL in children.

Adolescent↗

PubMed1996

Molecular cloning, tissue distribution, and chromosomal localization of human cationic amino acid transporter 2 (HCAT2).

Human cationic amino acid transporter 2 (HCAT2) was isolated from a human intestine cDNA library. The nucleotide sequence of the coding region predicts a 658-amino-acid protein with a calculated molecular weight of 71,669. As 91% of the residues are identical with those of the mouse cationic amino acid transporter 2 (MCAT2), HCAT2 seems to be a human counterpart of MCAT2. We found no isoform as was present in MCAT2. In Northern blot analysis, a single (9.0 kb) HCAT2 mRNA transcript was present in various human tissues. The highest level of expression was observed in skeletal muscle and the lowest level in the kidney. Hydropathy plots indicated that the translated protein is predicted to have 14 transmembrane domains with three potential N-glycosylation sites. Two patients with lysinuric protein intolerance (MIM No. 222700) were analyzed for HCAT2 cDNA but no mutation was detected. The HCAT2 gene was assigned to human chromosome 8p21.3-p22.

Amino Acid Metabolism, Inborn Errors↗

PubMed1996

Remodeling of HDL containing apoA-I but not apoA-II (LpA-I) by lipoprotein-deficient plasma and hepatic lipase: its effect on the structure and cellular cholesterol-reducing capacity of LpA-I.

We investigated the effects of lipoprotein-deficient plasma (LDP) and hepatic lipase (HL) on the structure and cellular cholesterol-reducing capacity of subclasses of LpA-I (HDL containing apoA-I but not apoA-II). LpA-I is composed of large (11.1 nm; L-LpA-I), medium (8.8 nm: M-LpA-I) and small (7.7 nm: S-LpA-I) particles. L-LpA-I and M- and S-LpA-I combined (MS-LpA-I) were incubated with lipoprotein-deficient plasma and HL in the presence of very low density lipoprotein (VLDL). After incubation of L-LpA-I, the proportions of cholesteryl esters and phospholipids decreased and as a result, the proportion of protein increased. The remodeled L-LpA-I particles were generally smaller (spherical: 7.8-8.8 nm) in diameter. A small number of disc-shaped particles were also found in electron photomicrographs. These changes coincided with a slower electrophoretic mobility of remodeled L-LpA-I. In the case of MS-LpA-I, only the proportion of free cholesterol increased after incubation, and MS-LpA-I particles did not change in size. The cholesterol-reducing capacities of remodeled L-LpA-I and MS-LpA-I from macrophage foam cell were slightly higher and lower than their respective original counterparts, although neither of these differences was statistically significant. These results suggest that LDP and HL mainly contribute to the remodeling of L-LpA-I particles, and may not affect the cellular cholesterol-reducing capacity of these particles.

Adolescent↗

PubMed1996

Prenatal monitoring in a family at high risk for ornithine transcarbamylase (OTC) deficiency: a new mutation of an A-to-C transversion in position +4 of intron 1 of the OTC gene that is likely to abolish enzyme activity.

DNA analysis of a male propositus with ornithine transcarbamylase (OTC) deficiency documented an A-to-C substitution in position +4 of intron 1. No other abnormalities were observed in the OTC gene, or at 563 bp upstream of the 5' site, which included a promoter region, or at 383 bp downstream of the termination codon, which included a polyadenylation signal sequence. This mutation produces an RsaI site in the sequence, which was used for prenatal monitoring in the fourth and fifth pregnancies. DNA from amniotic cells in the former case were positive for RsaI digestion and the SRY gene (sex determinant region Y), indicating hemizygosity for the mutant allele. OTC activity was not measurable, and mRNA of the OTC gene was not detected by Northern blotting in the affected fetal liver. RT-PCR (reverse transcription-PCR) demonstrated only the wild-type allele. Thus, the mutation interferes with RNA processing, and an extremely low amount of normally spliced mRNA for the OTC gene seems to have caused the disease in our patient. The fetus of the fifth pregnancy was a normal male, as confirmed postnatally.

Amino Acid Metabolism, Inborn Errors↗

PubMed1996

Correction of ornithine transcarbamylase deficiency in adult spf(ash) mice and in OTC-deficient human hepatocytes with recombinant adenoviruses bearing the CAG promoter.

Ornithine transcarbamylase (OTC) deficiency, the most common and severe inborn error of the urea cycle in humans, remains without adequate treatment, and mortality rates are high. Adenoviral vectors provide an efficient system for gene delivery, but there are problems, including toxicity. Efficient promoters that reduce the amount of vector required for treatment need to be developed. We constructed two recombinant adenoviral vectors, AdexCAGhOTC and AdexSR alpha hOTC, which harbor the human OTC gene under transcriptional control of CAG (a modified chicken beta-actin promoter with CMV-IE enhancer) and SR alpha (the SV40 early promoter with the R segment and part of the US segment of the HTLV-1 LTR), respectively. Each was tested in adult spf(ash) mice, an animal model of human OTC deficiency, and in primary human hepatocytes with OTC deficiency. Spf(ash) mice have a pronounced orotic aciduria as seen in humans. A complete recovery of hepatic OTC activity with minimal tissue damage was observed in these animals following the intravenous administration of AdexCAGhOTC alone. Western blot analysis confirmed hepatic OTC expression and normalization of orotic aciduria was evident for 60 days. Enzyme activities of primary human hepatocytes infected with AdexCAGhOTC were 10-40 times higher than those with AdexSR alpha hOTC. Thus, the adenoviral vector with an efficient promoter such as CAG, can be given further consideration for possible gene therapy in humans with OTC deficiency.

Actins↗

PubMed1996

Human ESP1/CRP2, a member of the LIM domain protein family: characterization of the cDNA and assignment of the gene locus to chromosome 14q32.3.

The LIM domain is present in a wide variety of proteins with diverse functions and exhibits characteristic arrangements of Cys and His residues with a novel zinc-binding motif. LIM domain proteins have been implicated in development, cell regulation, and cell structure. A LIM domain protein was identified by screening a human cDNA library with rat cysteine-rich intestinal protein (CRIP) as a probe, under conditions of low stringency. Comparison of the predicted amino acid sequence with several LIM domain proteins revealed 93% of the residues to be identical to rat LIM domain protein, termed ESP1 or CRP2. Thus, the protein is hereafter referred to as human ESP1/CRP2. The cDNA encompasses a 1171-base region, including 26, 624, and 521 bases in the 5'-noncoding region, coding region, and 3'-noncoding regions, respectively, and encodes the entire ESP1/CRP2 of 208 amino acids (M(r), 22,496). Human ESP1/CRP2 protein has two LIM domains, and each shares 35.1% and 77 or 79% identical residues with human cysteine-rich protein (CRP) and rat CRIP, respectively. Northern blot analysis of ESP1/CRP2 in various human tissues showed distinct tissue distributions compared with CRP and CRIP, suggesting that each might serve related but specific roles in tissue organization or function. Using a panel of human-rodent somatic cell hybrids, the ESP1/CRP2 locus was assigned to chromosome 14. Fluorescence in situ hybridization, using cDNA and a genome DNA fragment of the ESP1/CRP2 as probes, confirms this assignment and relegates regional localization to band 14q32.3.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic stem cells and B cells.

A receptor tyrosine kinase (RTK), TIE (tyrosine kinase that contains immunoglobulin-like loops and epidermal growth factor [EGF] homology domains), is expressed in vascular endothelial and hematopoietic cells. We generated monoclonal antibodies (MoAbs) against the extracellular domain of TIE and a polyclonal antibody against the TIE carboxyterminus and used them to analyze expression of TIE in hematopoietic cells. Western blotting detected two forms of TIE protein with a molecular mass of 135 and 130 kD in hematopoietic and endothelial cells. Northern blotting analysis revealed that TIE was expressed preferentially in undifferentiated cell lines, especially when megakaryocytic, but not erythroid differentiation was induced. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that TIE was predominantly expressed in the human hematopoietic progenitor fraction, CD34+ cells. Fluorescence-activated cell sorting (FACS) showed that 42% of CD34+ and 17% of KIT-positive (KIT+) cells were TIE-positive (TIE+). The majority (81%) of the primitive hematopoietic stem cells, CD34+CD38- cells, were TIE+. Assays of progenitor cells and long-term culture-initiating cells (LTC-IC) showed that the TIE+ fraction contained more primitive cells than the TIE- fraction. Some TIE+ cells were in the CD34- fraction, which were CD19+ and CD20+ (B cells). These findings indicate that TIE has a unique spectrum of expression in primitive hematopoietic stem cells and B cells. Although its ligand has not been identified, TIE and its ligand may establish a novel regulatory pathway not only in early hematopoiesis, but also in the differentiation and/or proliferation of B cells.

Animals↗

PubMed1996

The heparin-bound fraction of human lipoprotein-deficient serum inhibits endocytic uptake of oxidized low density lipoprotein by macrophages.

We recently demonstrated that bovine lactoferrin, a cationic whey protein from bovine milk, interacts with the negative charges of modified low density lipoproteins (modified LDL) such as acetylated LDL (acLDL) and oxidized LDL (oxLDL), which markedly interferes with their endocytic uptake by rat peritoneal macrophages (Kajikawa M, Ohta T, Takase M, Kawase K, Shimamura S, Matsuda I. Biochim Biophys Acta 1994;1213:82-90). In the present study, we examined whether human lipoprotein-deficient serum (LPDS) might contain protein(s) that could inhibit the endocytic uptake of oxLDL by mouse macrophages. We fractionated LPDS by heparin affinity chromatography and found that the cellular binding of oxLDL to mouse macrophages and subsequent endocytic uptake were inhibited by 50%-60% with the heparin-bound fraction, whereas the heparin-unbound fraction had no effect. Similar results were obtained in the experiments with acetylated LDL. Sephacryl S-300 gel-filtration chromatography of a mixture of oxLDL and the heparin-bound fraction revealed that a 150-kDa protein was associated with oxLDL. These results indicate that the electrostatic interaction of oxLDL with some component(s) of the heparin-bound fraction might interfere with the endocytic uptake of oxLDL by the macrophage scavenger receptor.

Animals↗

PubMed1996

Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA; MIM 256800) is an autosomal-recessive disorder characterized by recurrent episodes of unexplained fever, anhidrosis (absence of sweating) and absence of reaction to noxious stimuli, self-mutilating behaviour and mental retardation. The genetic basis for CIPA is unknown. Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. Mice lacking the gene for TrkA, a receptor tyrosine kinase for NGF, share dramatic phenotypic features of CIPA, including loss of responses to painful stimuli, although anhidrosis is not apparent in these animals. We therefore considered the human TRKA homologue as a candidate for the CIPA gene. The mRNA and genomic DNA encoding TRKA were analysed in three unrelated CIPA patients who had consanguineous parents. We detected a deletion-, splice- and missense-mutation in the tyrosine kinase domain in these three patients. Our findings strongly suggest that defects in TRKA cause CIPA and that the NGF-TRKA system has a crucial role in the development and function of the nociceptive reception as well as establishment of thermoregulation via sweating in humans. These results also implicate genes encoding other TRK and neurotrophin family members as candidates for developmental defect(s) of the nervous system.

Amino Acid Sequence↗

PubMed1996

Three brothers with progressive hepatic dysfunction and severe hepatic steatosis due to a patent ductus venosus.

Three Japanese brothers with progressive deterioration of hepatic function and fatty degeneration of the liver eventually leading to hepatic encephalopathy were recently encountered. Each of them had a congenital intrahepatic portosystemic venous shunt due to a patent ductus venosus. Liver dysfunction and hepatic steatosis reverted to normal with surgical correction of the ductus venosus. Our observations suggest that impairment of liver function occurs first in the presence of malnutrition related to a reduction of blood in the portal vein. Hepatic steatosis is a consequence of a depleted metabolism of hepatocytes. Congenital portosystemic venous shunt due to a patent ductus venosus in this family has a genetic background.

Angiography↗

PubMed1996

Zinc status relates to hematological deficits in women endurance runners.

OBJECTIVE: We investigated zinc (Zn) status and effect of Zn supplementation in relation to iron deficiency anemia in Japanese female endurance runners in an attempt to define the role of Zn in hematologic abnormalities. METHODS: After estimating zinc status based on total body zinc clearance (ClZn), 21 women runners were divided into two groups: one group was of normal Zn status (group A), and the other was a Zn deficient group (group B). We then compared the hematological status in both groups, before and after iron or iron plus Zn supplementation. RESULTS: Number of red blood cells (RBC), serum concentrations of hemoglobin (Hb), iron and total protein in Group A were significantly higher than those in Group B, while serum Zn levels were similar in both groups. There was a significantly positive correlation between ClZn and total protein, and hemoglobin in all subjects. After combined treatment with ferrous citrate and zinc sulfate, the concentrations of total protein, iron, RBC, and Hb were significantly increased in the four Zn deficient runners. CONCLUSION: Zn status to some extent can account for hematological abnormalities in female endurance runners.

Adult↗

PubMed1996

Phylogenetic analysis of Streptomyces spp. causing potato scab based on 16S rRNA sequences.

The complete 16S rRNA sequences of 12 strains of Streptomyces spp., including potato scab pathogens, were determined. Among the strains of Streptomyces scabies that were isolated from diverse geographical areas and differed in melanoid pigment production, either no difference or one difference in sequence was observed. The sequence of S. scabies was most similar to the sequences of Streptomyces diastatochromogenes, Streptomyces bottropensis, and Streptomyces neyagawaensis, which belong to the Diastatochromogenes group. The levels of similarity of the 16S rRNA sequences of Streptomyces acidiscabies and S. scabies were almost the same as the levels of similarity between S. acidiscabies and other Streptomyces strains. Streptomyces sp. strain 91-Sy-13, which was isolated in Japan from potato scab and belongs to a distinct species on the basis of phenotypic characteristics and DNA relatedness, exhibited lower levels of 16S rRNA sequence similarity with other potato scab pathogens, as well as other Streptomyces species. The phylogenetic tree constructed on the basis of 16S rRNA sequence data showed that the Streptomyces spp. that cause potato scab composed unique branches. The results of our phylogenetic analysis based on complete 16S rRNA sequences confirmed the lack of close relationships among Streptomyces spp. that cause potato scab. Our findings suggest that potato scab is caused by phylogenetically diverse Streptomyces species and that the pathogenicities of these organisms developed independently.

Base Sequence↗

PubMed1996

Gene therapy for ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency in humans is the most common and severe inborn error of the urea cycle. Despite therapeutic advances, OTC deficiency remains without adequate treatment, hence mortality rates are high. In the two available strains of OTC-deficient murine models, spf and spfash, researchers have tried to make genetic corrections by introducing the OTC gene. Transient but complete recovery of OTC was obtained in adult spfash mice and in OTC-deficient human primary hepatocytes, using a recombinant adenoviral vector. These experiments represent a first step in the development of human gene therapy for OTC deficiency and other hepatic enzyme deficiencies.

Adenoviridae↗

PubMed1996

Phenotypic variability in male patients carrying the mutant ornithine transcarbamylase (OTC) allele, Arg40His, ranging from a child with an unfavourable prognosis to an asymptomatic older adult.

In five different Japanese families, we identified six male hemizygotes (aged 6, 9, 15, 17, 56, and 65 years) and a putative candidate (aged 48 years), carrying a mutant allele of the ornithine transcarbamylase (OTC) gene, a G to A substitution at nucleotide 119 in exon 2 generating histidine in place of arginine. OTC activity in the necropsied liver tissue was reduced to approximately 12% of the control and that of COS 1 cells transfected with Arg40His OTC cDNA was 10.2 +/- 1.8% of the control transfected with wild type OTC cDNA. Clinical features ranged from death during a hyperammonaemic attack (a 9 year old) to a 65 year old asymptomatic man. We consider that the amount of protein ingested by these subjects may be one predisposing factor leading to the manifestation of this disease.

Adolescent↗

PubMed1996

[Nasopharyngeal natural killer cell lymphoma with pericardial infiltration].

A 77 year-old woman was admitted to the hospital because of nasal obstraction on March 1994. Tumorectomy of the nasopharyngeal tumor disclosed non-Hodgkin's lymphoma (LSG : diffuse, medium sized). The patient was treated with local radiotherapy to nasopharyngeal region and combined chemotherapy (2 courses of CHOP) to reduce residual tumor. On July, the pericardial effusion appeared and the large granular lymphocyte (LGL) like lymphoma cells were observed in the effusion. Flow cytometic analysis of these cells showed that they expressed CD 2, CD 7, CD 56 and HLA-DR, but did not express CD 3. T-cell receptor gene (TCR beta) rearrangement was not observed and natural killer activity was detected in these lymphoma cells. The patient was treated with ProMACE and the pericardial infusion of methotrexate, carboplatin and prednisolone, but the patient died of heart failure. Monoclonarity of lymphoma cells in the pericardial effusion was determined by southernblot analysis, using the terminal repeat of Epstein-Barr virus (EBV) for probe. It was suggested that EBV participated in tumorgenesis in this case.

Aged↗

PubMed1996

[Detection of PEBP2 beta/MYH11 fusion mRNA in acute myelomonocytic leukemia without marrow eosinophilia].

We present a 15-year-old woman with acute myelomonocytic leukemia without marrow eosinophilia, M4 in the FAB classification. She was admitted to our hospital with nausea and headaches. Upon admission, the leukocyte count was 284,000/microliters with 95% leukemic cells. The bone marrow aspirate was hypercellular with 74.8% blasts and 0.2% eosinophils. Leukemic cells were positive for myeloperoxidase and esterase staining. Initially, the karyotype of the bone marrow cells on admission was considered to be normal. However, the PEBP2 beta/MYH11 fusion transcript was detected in the bone marrow mononuclear cells by using the reverse transcriptase-polymerase chain reaction (RT-PCR). Reevaluation of karyotypes showed a t(16;16) (p13;q22) in the bone marrow cells. After achieving complete remission, she was treated with low-dose etoposide. Chromosome analysis showed a normal karyotype and no amplified chimeric transcripts were observed. This case indicates that the molecular analysis of PEBP2 beta and MYH11 genes is a useful tool to detect inv (16) and t(16;16) which were often difficult to find, and that leukemic cells from some cases of M4 without marrow eosinophilia have these chromosome abnormalities.

Adolescent↗

PubMed1996

[A nation-wide survey for neurologic and hepato-neurologic type of Wilson disease: clinical features and hepatic copper content].

A nation-wide survey for Wilson disease was performed from 1990 to 1991. We studied clinical features and copper content in liver for the neurologic and hepato-neurologic types. A questionnaire was sent to more than five thousand hospitals in Japan. Thirty-three percent of physicians completed the questionnaire. Four hundred and twenty-five cases were studied for the onset age, primary symptoms, prognosis and hepatic copper content. The onset age of neurologic and hepato-neurologic type of Wilson disease was usually 6 years or older. The most common initial symptom was dysarthria. Gait disturbance, flapping tremor and Kayser-Fleischer rings were also very common symptoms. We conclude that in patients with dysarthria and/ or extra pyramidal symptoms over 6 years of age, Wilson disease should be considered. The prognosis quod vitam of patients with neurologic and hepato-neurologic Wilson disease is not always fatal. However, many patients required prolonged treatment at either a hospital, sanatorium or at home due to irreversibility of their severe neurological defects. This result shows that early detection is the most important factor for a promising prognosis. Copper content in liver was examined for each type of Wilson disease. Neurologic type of Wilson disease had the highest copper content, followed by hepato-neurologic type. Hepatic type had the lowest copper level out of these three forms of the disease. The mechanism of onset for each type of Wilson disease should be studied using these results.

Adolescent↗

PubMed1996

[Rearrangements of immunoglobulin heavy chain gene in Waldenstr"om's macroglobulinemia].

We investigated rearrangements of immunoglobulin heavy chain (Ig(H)) gene of the bone marrow mononuclear cells by Southern hybridization in 7 patients with Waldenström's macroglobulinemia. Three of 7 cases showed the rearrangement of Ig (H) gene. The cases with Ig (H) gene rearrangements showed high rates of CD19 and CD20 positive cells compared to the cases with no rearrangements. Two out of 3 cases included less than 3 g/dl IgM. On the other hand, 4 cases without rearrangements had lower percentage of B cells in the bone marrow and higher serum IgM (4/4; more than 3g/dl) than the cases with the rearrangements. Thus, the rearrangements of Ig (H) chain gene did not correlate with serum IgM level and related to the quantity of B cells in the bone marrow in WM.

Aged↗