Biomedical subjects

T Matsuguchi

Publications and source records attributed to T Matsuguchi.

At least 55 records · Page 3Linked to original sources

PubMed1992

Aplastic anemia in a male with loss of the Y chromosome.

We carried out chromosomal analysis of a 33-year-old male who was diagnosed as having aplastic anemia. The patient showed severe pancytopenia, a normal NAP score, hypoplastic marrow and no myelodysplastic changes. 45,XO was found in all bone marrow cells examined, and in 10% of peripheral blood cells examined. To our knowledge, this is the first reported case of male aplastic anemia to show loss of the Y chromosome in all bone marrow cells examined, and this case may suggest a possible mechanism of juvenile onset of aplastic anemia.

Adult↗

PubMed1991

The presence and active transcription of three independent leader exons in the mouse insulin-like growth factor II gene.

The presence of multiple leader exons is one of the common features in the insulin-like growth factor II (IGFII) genes. Among them the 5' most exon sequence, rE1, was so far reported to be present only in the rat genome. We have found a rE1-homologous sequence in the mouse genome (mE1) and have isolated it by genomic cloning. The mE1 sequence was located in the 5' region of the IGFII gene and was considered to take an integral part in the mouse IGFII gene construction, just like in the rat gene. Overall homology between mE1 and rE1 regions was approx. 95%. The mE1 was actively transcribed in the newborn tissues and generated approx. 3.8 kb RNA species. Since the other two leader exon sequences were also active, producing 4.6 kb and 3.6 kb RNA species, respectively, transcription units of the mouse IGFII gene were, thus, composed of three leader exon systems.

Animals↗

PubMed1991

Genomic organization of the alpha chain of the human C4b-binding protein gene.

C4b-binding protein (C4bp) is a serum glycoprotein that is one of the regulators of the complement activation (RCA) family. This protein is composed of structurally related 70-kDa (alpha chain) and 45-kDa (beta chain) polypeptides. The alpha chain of C4bp (C4bp alpha) consists of eight short consensus repeats (SCR), which constitute the amino-terminal 491 residues. Human C4bp is also one of the acute-phase reactants. In order to clarify the genetic basis of the SCR and to understand the regulatory mechanisms of C4bp synthesis, we isolated 6 genomic DNA clones covering all of the human C4bp alpha gene. This gene consists of 12 exons and spans about 40 kb. Each of the SCRs is encoded by a single exon, except for the second SCR (SCR II), which is encoded by two separate exons, demonstrating that human C4bp alpha has a split SCR at the genomic level. The 5' flanking region was sequenced up to 380 bases upstream from the putative transcription initiation site. Several possible binding sites for transcription factors were identified.

Base Sequence↗

PubMed1991

Constitutive production of granulocyte colony-stimulating factor and interleukin-6 by a human lung cancer cell line, KSNY: gene amplification and increased mRNA stability.

A human lung squamous cell carcinoma cell line designated KSNY was established from a patient suffering from marked neutrophilia and polyclonal hyper-gamma-globulinemia. In our previous report, we demonstrated colony-stimulating activities in the culture supernatant of this cell line. To determine the exact molecules for the activities, we investigated the gene expression of various cytokines in KSNY cells and showed the mRNA expression of both granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6). We also detected substantial amounts of G-CSF and IL-6 in the culture supernatant with sensitive enzyme-linked immunosorbent assays (ELISA). The amplification of the gene locus for G-CSF, but not for IL-6 was shown by Southern blot analysis. Furthermore, we also showed that the mRNAs for G-CSF and IL-6 were relatively stable in KSNY cells. These findings are thought to be related to the constitutive production of the cytokines in KSNY cells.

Blotting, Northern↗

PubMed1991

Interleukin 6 and tumor necrosis factor fully activate liver-specific gene expression of the alpha chain of C4b-binding protein.

We investigated the gene expression of the alpha chain of C4b-binding protein (C4bp alpha) in a variety of tissues, and in liver cell and hepatoma lines. C4bp alpha mRNA was detected in the liver, but not in the other tissues examined. The constitutive gene expression of C4bp alpha by a hepatoma line, HepG2, was significantly augmented by treatment with monocyte-conditioned medium (MoCM), 12-O-tetradecanoylphorbol-13-acetate (TPA), interleukin-6 (IL6) and tumor necrosis factor (TNF) but not by a calcium ionophore (A23187) or interleukin-1 beta (IL1 beta).

Blotting, Northern↗

PubMed1990

Production of interleukin 6 from human liver cell lines: production of interleukin 6 is not concurrent with the production of alpha-fetoprotein.

The production of interleukin (IL) 6 from six human liver cell lines, including Chang liver, HLF, HLE, HepG2, PLC/PRF/5, and HuH-7, was investigated using enzyme-linked immunosorbent assay and Northern blot analysis. When cells were cultured in the presence of 12-O-tetradecanoylphorbol-13-acetate, significant amounts of IL6 were detected in the culture supernatants of Chang liver cells, HLF cells, and HLE cells. However, IL6 was not detected in the culture supernatants from HepG2 cells, PLC/PRF/5 cells, or HuH-7 cells which had been treated similarly. To further investigate the production of IL6, expression of the IL6 gene was studied. Results of Northern blot analysis using IL6 complementary DNA as a probe showed that the induction was initiated at the mRNA level. Moreover, IL6 mRNA was also induced by IL1 beta and tumor necrosis factor but not by a calcium ionophore (A23187) or IL6 itself in Chang liver cells. This is the first study to demonstrate the production of human IL6 in liver cells. Furthermore, when the production of alpha-fetoprotein (AFP) from the liver cell lines was examined, the three that were able to produce IL6 failed to produce AFP, whereas the other three cell lines succeeded in producing AFP. These observations may indicate the heterogeneous origin of the liver cell lines.

Adolescent↗

PubMed1990

The primary structure of the rat insulin-like growth factor II gene region.

Complete nucleotide sequences of the rat insulin-like growth factor II gene region including 5' 18 kilobases (kb) up to the insulin gene, all exonic and intronic, and 3' 6 kb sequences were determined. Among these sequences several repetitive stretches became evident besides integration of type II Alu and identifier sequences. They were: (1) twelve repetitions of about 100 base pair (bp) units; (2) duplication of 60 bp units; (3) triplication of a 24 bp unit; and (4) 41-fold expansion of 12-15 bp units.

Animals↗

PubMed1990

Functional analysis of multiple promoters of the rat insulin-like factor II gene.

We have characterized the multiple promoters of the rat insulin-like growth factor II (rIGFII) gene by in vivo transient expression assay using a series of deletion mutant templates. Among the four promoters (P1, P2, P3 and P6), two (P2 and P3) showed relatively strong promoter activities compared with the other two. One of the four promoters, P2, was further characterized by gel band-shift and footprinting analysis using HeLa cell nuclear extract, showing two retarded bands and at least one protected sequence stretch. The results indicated that P2 has a very simple structure like P3, and consists of no more than 141 base-pairs (bp) including a TATA box and two GC core hexanucleotides. Promoter strength shown by in vivo transient expression in different cell types failed to explain the differential employment of P2 and P3 in these cells, suggesting the involvement of other regulatory mechanisms that might operate only in the native state.

Animals↗

PubMed1990

Muroctasin [MDP-Lys(18)] augments the production of granulocyte colony-stimulating factor (G-CSF) from human peripheral blood mononuclear cells in vitro.

N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-Lysine (MDP-Lys(L18), muroctasin) is an immunopotentiating substance. Neutrophilia and elevated levels of colony-stimulating factor (CSF) in peripheral blood were previously found after the administration of this compound in both mice and humans. To specify the type of CSF and to elucidate the mechanisms of the neutrophilia, we cultured human peripheral blood mononuclear cells (PBMC) in the presence of muroctasin and measured the levels of granulocyte CSF (G-CSF) in the culture supernatants using our sensitive enzyme-linked immunosorbent assay. G-CSF is an active hematopoietic growth factor specific for cells of a neutrophilic lineage, and muroctasin was found to significantly augment the G-CSF production from PBMC in vitro (P less than 0.01). Furthermore, production of G-CSF from human PBMC in the presence of muroctasin was also supported by the Northern blot analysis using cDNA encoding G-CSF as a probe.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1989

Molecular cloning of the cDNA coding for proline-rich protein (PRP): identity of PRP as C4b-binding protein.

Proline-rich protein (PRP) is a plasma protein with a high proportion of proline residues and possessing lipid-binding properties. In order to clarify its structure, a human liver cDNA library was screened using anti-PRP antiserum. Several overlapping phage cDNA clones were isolated and the total nucleotide sequence of the cDNA, 2178 bp in length, was analyzed. The amino acid composition of PRP deduced from the cDNA was essentially the same as that reported for PRP. In a homology search, the cDNA sequence was almost completely the same as the previously reported cDNA sequence of C4b-binding protein. Furthermore, the reported molecular weights of the two proteins under both reduced and unreduced conditions were quite alike. These findings indicate that PRP is identical with C4bp.

Amino Acid Sequence↗

PubMed1989

Multiple polyadenylation sites in a large 3'-most exon of the rat insulin-like growth factor II gene.

The rat insulin-like growth factor II (rIGFII) gene produces, in addition to three major mRNA species 3.6 kilobases (kb), 4.6 kb and 3.8 kb in length which represent transcripts from three independent leader-exons, multiple smaller-sized products that distribute broadly in the 1-3 kb region on Northern blots. Structural constituents of these RNAs were analyzed by hybridization with region-specific probes prepared from the entire rIGFII genome. Most of these shorter RNAs contained both 5'-untranslated and coding regions, but only parts of the 3'-untranslated region. At least nine protected sites were mapped within a single 3'-most exon E6 by S1 nuclease analysis. Some but not all of these sites were associated with the upstream polyadenylation signal, AATAAA, or its variants. Since none of the shorter subspecies contained intronic sequences, aberration in splicing is not involved in their generation. Thus, the main parts of submature materials are a collection of discrete species of RNAs, most, if not all, of which are produced by alternative polyadenylation site selection.

Amino Acid Sequence↗

PubMed1989

A novel transcription unit within the exon sequence of the rat insulin like growth factor II gene.

We identified a transcription unit within a single exon of the rat insulin like growth factor II (rIGFII) gene by a combination of Northern blotting, S1 nuclease mapping and primer extension analyses. Among multiple mRNA products of rIGFII, the 1.8kb transcript has a discrete 5' terminus and is encoded exclusively in a single 3'-extreme exon with no trace of the coding region. The upstream region of the 5' terminus contains a completely matching GC-rich 16bp palindrome and several sequence motifs highly homologous to the consensus sequences of binding sites for transcriptional regulatory proteins AP2, H2TF1 and NF-kappa B.

Animals↗

PubMed1988

Transcriptional deviation of the rat insulin-like growth factor II gene initiated at three alternative leader-exons between neonatal tissues and ascites hepatomas.

Insulin-like growth factor II (IGFII) is a mitogenic polypeptide, the mRNAs of which are present in multiple forms, despite derivation from a single gene. In the present study, we observed nearly full-length rat IGFII mRNA structures of major species with three alternative 5'-untranslated sequences and a common unusually-long 3'-untranslated region. These three 5' sequences (E1, E2 and E3) locate at different sites on the rat IGFII genome and are therefore independent leader-exons. Northern blotting using probes specific to E1, E2 and E3 sequences revealed major bands at 3.8 kilobases (kb), 4.6 kb and 3.6 kb in nucleotide length, respectively. The E1, E2 and E3 promoters were functional in all rat neonatal tissues examined and in the adult brain, and the relative level of mRNA species was fairly constant, although the bulk expression varied from tissue to tissue. Thus, the three mRNAs initiated from the single rat IGFII gene are co-ordinately regulated. However, this relative transcriptional constancy deviated variously in several lines of transplantable rat ascites hepatomas, thereby indicating that each mRNA level can also be regulated independently.

Amino Acid Sequence↗

PubMed1988

Reactivation of rat insulin-like growth factor II gene during hepatocarcinogenesis.

The insulin-like growth factor II (rIGFII) is a mitogenic polypeptide, the expression of which is high in most rat tissues during embryonic development, yet is barely detectable in adult tissues except for some of neurogenic origin. The gene is present as a single copy in the genome but has three alternative leader exons, E1, E2 and E3, thereby with three independent transcriptional promoters. We analysed the expression of rIGFII and the relative efficiency of each promoter in hepatocarcinogen-treated livers, primary hepatomas and established hepatoma lines. The E3-specific product was first detected after 6 weeks of 3'-methyl-4-dimethylaminoazobenzene treatment and those of E1 and E2 also after 9 weeks. The levels gradually increased according to the sum of the treatment period, but reactivation was nil in the regenerating liver. Consistently high levels of expression were observed in all primary tumors, but the relative promoter activity varied with the tumor. The significance of rIGFII reactivation was discussed in the light of the hepatocarcinogenesis.

Animals↗

PubMed1988

Prevention of vasospastic angina by alcohol ingestion: report of 2 cases.

The authors report 2 patients with vasospastic angina in whom alcohol ingestion was effective in preventing angina. Coronary angiography revealed no organic coronary stenosis but demonstrated coronary artery spasm during angina attacks. In 1 patient, alcohol ingestion every six hours completely suppressed frequent spontaneous angina. In the other patient, alcohol ingestion markedly prolonged the duration of the exercise on treadmill testing by preventing exercise-induced coronary spasm.

Alcoholic Beverages↗

PubMed1987

A new leader exon identified in the rat insulin-like growth factor II gene.

In the rat insulin-like growth factor II gene, we identified an alternative 5'-untranslated sequence, in addition to the two sequences documented recently (1986) J. Mol. Biol. 192. 737-752, (1986) J. Biol. Chem. 261. 17138-17149. This sequence was encoded in an extreme 5' separate exon (E1 exon), the promoter region of which could be distinguished from others by features including lack of the TATA-box and GC-repeat, and heterogeneity in the transcriptional initiation.

Animals↗

PubMed1987

Effects of nicorandil on rest and effort angina unresponsive to combination therapy with a calcium antagonist and oral nitrate.

The efficacy of nicorandil, a new anti-anginal agent, was evaluated in 11 patients with rest and effort angina not inhibited by combination therapy with a calcium antagonist and an oral nitrate. Electrocardiographic findings during an attack demonstrated ST depression in seven patients, ST elevation in three, and either elevation or depression in two. Coronary angiography in nine patients revealed significant stenosis (greater than or equal to 75%) in eight. Angina persisted in all 11 patients in spite of treatment with 120 to 360 mg/day of diltiazem or 80 mg/day of nifedipine plus 20 to 160 mg/day of isosorbide dinitrate. Three patients were receiving beta-blocker as well; seven were receiving antiplatelet therapy. During combination therapy, patients had between 3.7 and 25 anginal attacks per week (mean +/- SD, 12.2 +/- 6.9). When nicorandil in a dosage of 20 to 40 mg/day was added to the regimen, the mean number of attacks dropped significantly (P less than 0.01) to 1.4 +/- 1.8 times/week. Two patients did not respond to nicorandil. When placebo was substituted for nicorandil in eight of nine responders, the frequency of attacks increased significantly (P less than 0.05) from 0.6 +/- 0.7 to 6.7 +/- 4.8 times/week. Nicorandil did not affect heart rate or blood pressure. These results suggest that nicorandil inhibits rest and effort angina unresponsive to usual doses of calcium antagonist and oral nitrate.

Aged↗

PubMed1986

Diagnosis of important fixed coronary stenosis in patients with variant angina by exercise tests after treatment with calcium antagonists.

A 12 lead electrocardiogram was recorded during treadmill exercise in 57 patients with variant angina in whom coronary angiography was performed. Thirty six patients performed exercise tests with and without calcium antagonists, and 21 performed them only with calcium antagonists. In 55 patients calcium antagonists had prevented spontaneous attacks of variant angina for more than two days before the test. The other two patients were given a single dose of diltiazem (90 mg) two hours before the test. Exercise testing without calcium antagonists induced ST segment elevation with chest pain in nine patients, ST segment depression in 10 (nine with chest pain), and no important shift of the ST segment in 17. Five patients had severe coronary stenosis (greater than or equal to 75%) and all of them showed positive response. Thirty one patients had no important coronary stenosis and 14 of them showed positive response. The sensitivity of the exercise test in detecting a coronary stenosis greater than or equal to 75% was 100% without calcium antagonists but the specificity was low (55%). When the exercise test was done in patients taking calcium antagonists, only two (specificity 96%) of 48 patients without severe coronary stenosis showed positive response (elevation of ST segment in one and depression in another) whereas all nine patients with severe coronary stenosis had a positive response (depression of ST segment in six and elevation in three (sensitivity 100%). It is concluded that exercise testing with calcium antagonists may be a useful method for detecting severe coronary stenosis in patients with variant angina.

Adult↗