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T Noguchi

Publications and source records attributed to T Noguchi.

At least 361 records · Page 20Linked to original sources
PubMed1997

[Effects of olprinone on IL-6 and IL-10 production during and after cardiac surgery].

Phosphodiesterase inhibitor (PDEI) has been accepted as an inodilator with positive inotoropic and vasodilating actions. Recently many new PDEIS have been available for the treatment of heart failure. We investigated the effect of a new PDEI-III agent, olprinone, on IL-6 and IL-10 production during and after coronary bypass graft surgery (CABG). Twelve patients scheduled for CABG were assigned to 2 groups. In 6 patients (Group-O), olprinone was administered continuously for 30 minutes at a rate of 0.3 micrograms.kg-1.min-1 (gamma) after the anesthesia induction. Then, the infusion rate of olprinone was decreased to 0.2 gamma and it was kept until the 3rd post-operative day. In another 6 patients (Group-C), phentolamine was used for vasodilator instead of olprinone. The plasma levels of IL-6 in Group-O did not show any significant change during perioperative period, whereas those in Group-C reached the peak at the end of extracorporeal circulation and did not recover to control level until the 3rd post-operative day. The plasma levels of IL-10 in Group-O increased to the maximum level at the end of extra-corporeal circulation and were significantly higher than those in Group-C. It is suggested that olprinone has not only inodilating action but also anti-inflammatory action at therapeutic concentrations used for heart failure.

Cardiac Surgical Procedures↗
PubMed1997

[A new surgical management of esophageal stenosis without esophagectomy].

In many cases, reflux esophagitis following surgical treatment for esophageal stenosis is caused by the recurrence of that after esophagectomy and esophogogastrostomy. We performed a new management without esophagectomy for a 66-year-old man with sliding hiatal hernia and esophageal stenosis induced by reflux esophagitis. A Expanding Metalic Stent (MES) was inserted to the stenotic portion of the esophagus, and then Collis-Nissen's procedure was done through left thoracotomy and phrenotomy. The postoperative course was satisfactory, and no gastroes-ophageal reflux was detected with the use of 24h pH-monitoring of the esophagus after surgery.

Aged↗
PubMed1996

Resonance Raman evidence that photodissociation of nitric oxide from the non-heme iron center activates nitrile hydratase from Rhodococcus sp. N-771.

Nitrile hydratase (NHase) from Rhodococcus sp. N-771, which contains a non-heme iron center in the catalytic site, has been known to be activated by light illumination. Recently, endogenous nitric oxide (NO) was found in this enzyme by FTIR spectroscopy [Noguchi et al. (1995) FEBS Lett. 358, 9-12]. In order to directly detect the bonding between NO and the iron atom and the reaction of NO upon photoactivation, resonance Raman spectra of the NHase were measured with 413 nm excitation at 85 K. Two prominent bands at 592 and 570 cm-1 were observed in the inactive from, and both of them were completely lost upon photoactivation. Upon subsequent introduction of 15NO, the active NHase was converted to the inactive form again and the above two bands were restored with downshifts by 10 and 12 cm-1, respectively. Also, the excitation profiles of these bands in the 350-500 nm region mostly followed the absorption spectrum arising from the iron center. From these isotopic shifts and the excitation profiles, the two Raman bands were assigned to the Fe-NO stretching and bending vibrations that are probably coupled with each other. The results provided solid evidence that NO is bound to the non-heme iron in the inactive NHase and its photodissociation activates the enzyme.

Binding Sites↗
PubMed1996

Metabolism of glyoxylate, the end product of purin degradation, in liver peroxisomes of fresh water fish.

In marine fish liver, degradative enzymes able to convert purines to urate have been shown to be located in the cytosol and degradative enzymes able to convert urate to urea and glyoxylate in the peroxisomes. The end products of purine degradation are urea and glyoxylate in fish. Glyoxylate may be converted to glycine by alanine:glyoxylate aminotransferase for the reutilization of purine carbons. The present report describes that hepatic alanine:glyoxylate aminotransferase is located both in the peroxisomes and in the mitochondria in fresh water fish, showing that the intracellular localization of the enzyme differs between fresh water fish and marine fish. This is the first report on the presence of alanine:glyoxylate aminotransferase in fish peroxisomes.

Acid Phosphatase↗
PubMed1996

Electronic and vibrational structure of the radical cation of P840 in the putative homodimeric reaction center from Chlorobium tepidum as studied by FTIR spectroscopy.

Light-induced FTIR difference spectra of P840 upon its oxidation (P840+/P840) have been measured with the reaction center complex from the green sulfur bacterium Chlorobium tepidum. A broad band centered near 2500 cm-1 was observed in P840+, which is comparable to the band near 2600 cm-1 previously observed in P870+ of purple bacteria and assigned to the electronic transition in the bacteriochlorophyll a (BChla) dimer (Breton et al. (1992) Biochemistry 31, 7503-7510]. The intensity of this electronic band found in P840+ was about the same as that in P870+. The P840+ spectrum also showed several intensified vibrational modes, which are characteristic of the P870+ spectrum as well. These similar features of the electronic transition and the intensified lines indicate that P840+ is a BChla dimer whose electronic structure is similar to P870+. Based on the previous theoretical works, the possibility that P840+ has an asymmetric structure as P870+ was suggested. Also, two strong positive bands at 1707 and 1694 cm-1 probably assigned to the keto C9 = O stretching modes of P840+ were observed in the P840+/P840 spectrum. Three different interpretations are possible for the presence of the two C9 = O bands: (i) P840+ is an asymmetric dimer cation. (ii) P840+ has a symmetric structure, and the time constant of positive charge exchange between the two BChla molecules coincides with that of IR spectroscopy (10-13 s). (iii) The electric field produced by the positive charge on P840+ affects the C9 = O frequency of the neutral BChla in P840+ itself (when the charge exchange time is slower than the time scale of 10-13 s) or of a BChla in the close proximity of P840+. The negative bands at 1734 and 1684 cm-1 were assigned to the ester C10 = O and the keto C9 = O of neutral P840, respectively, both of which are free from hydrogen bonding. These results and interpretations regarding the structural symmetry and the molecular interactions of P840 and P840+ are discussed in the framework of the "homodimeric" reaction center of green sulfur bacteria.

Chlorobi↗
PubMed1996

Synthesis and biological activity of conformationally restricted analogs of milnacipran: (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxami de, an efficient noncompetitive N-methyl-D-aspartic acid receptor antagonist.

We recently demonstrated that (+/-)-(Z)-2-(aminomethyl)-1-phenyl-N,N-diethylcyclopropanecarboxamide [milnacipran, (+/-)-1], an inhibitor of the reuptake of serotonin (5-HT), was a noncompetitive NMDA receptor antagonist. On the basis of the cyclopropane structure of (+/-)-1, conformationally restricted analogs with different stereochemistries, namely 1-phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamindes (2, 3, ent-2, and ent-3), were designed and synthesized. Among these analogs, 2a, 2b, and 2f, with (1S,2R,1'S)-configuration, were more efficient than milnacipran as NMDA receptor antagonists; these compounds significantly inhibited the binding of [3H]MK-801 at IC50 = 0.35 +/- 0.08, 0.20 +/- 0.024, and 0.16 +/- 0.02 microM, respectively, and blocked the response of voltage-clamped oocytes to NMDA, surpassing the effects of (+/-)-1. Although both the 1'-methyl analog 2a and the 1'-vinyl analog 2f, like (+/-)-1, strongly inhibited 5-HT uptake in vitro, the corresponding 1'-ethyl analog 2b was devoid of the inhibitory effect on 5-HT uptake, while it was about 30 times more potent as an NMDA receptor antagonist than (+/-)-1.

Animals↗
PubMed1996

Characterization of a 115-kDa protein that binds to SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in Chinese hamster ovary cells.

SH-PTP2, a non-transmembrane-type protein-tyrosine phosphatase with two Src homology 2 domains, was previously shown to play a positive signaling role in the insulin-induced activation of Ras and mitogen-activated protein kinase. SH-PTP2 was shown to associate with a 115-kDa tyrosine-phosphorylated protein (pp115), as well as with insulin receptor substrate 1, in insulin-stimulated Chinese hamster ovary cells that overexpress human insulin receptors (CHO-IR cells). In vivo and in vitro binding experiments revealed that SH-PTP2 bound to pp115 through one or both of its SH2 domains. The pp115 protein was partially purified from insulin-stimulated CHO-IR cells that overexpress a catalytically inactive SH-PTP2 by a combination of immunoaffinity and lectin-affinity chromatography. A monoclonal antibody to pp115 was then generated by injecting the partially purified protein into mice. Experiments with this monoclonal antibody revealed that pp115 is a transmembrane protein with a domain exposed on the cell surface and that it binds to SH-PTP2 in response to insulin. The insulin receptor kinase appeared to phosphorylate pp115 on tyrosine residues both in vivo and in vitro. The extent of tyrosine phosphorylation of pp115 associated with SH-PTP2 was greatly increased in CHO-IR cells that overexpress catalytically inactive SH-PTP2 compared with that observed in CHO-IR cells overexpressing wild-type SH-PTP2. Furthermore, recombinant SH-PTP2 preferentially dephosphorylated pp115 in vitro, indicating that SH-PTP2 may catalyze the dephosphorylation of phosphotyrosine residues in pp115 after it binds to this protein. These results suggest that pp115 may act as a transmembrane anchor to which SH-PTP2 binds in response to insulin. Furthermore, pp115 may be a physiological substrate for both the insulin receptor kinase and SH-PTP2.

Animals↗
PubMed1996

Tyrosine phosphorylation is crucial for growth signaling by tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2).

[3H]Thymidine (TdR) incorporation by human osteosarcoma cell line MG-63 was significantly stimulated at as early as 3 h after the addition of either TIMP-1 or TIMP-2 alone. Maximum stimulation was attained at a concentration of either 20 ng/ml (0.71 nM) TIMP-1 or 1.0 ng/ml (46 pM) TIMP-2. Tyrosine kinase inhibitors such as genistein, erbstatin, and herbimycin A almost completely inhibited the [3H]TdR incorporation stimulated by either of the TIMPs. However, essentially no effect was observed with H-89, H-7, bisindolylmaleimide and K-252a. These inhibition studies suggest a crucial role for tyrosine kinase in the signal transduction of TIMPs. Phosphotyrosine-containing proteins were significantly elevated by the treatment with both TIMPs. We also found that either TIMP stimulated an increase in mitogen-activated protein (MAP) kinase activity, suggesting that MAP kinase plays a role in TIMP-dependent growth signaling.

Benzoquinones↗
PubMed1996

Re-evaluation of chromosomal aberration induction on nine mouse lymphoma assay "unique positive' NTP carcinogens.

In a collaborative study organized under the JEMS MMS, nine mouse lymphoma assay (MLA) "unique positive' NTP rodent carcinogens were re-evaluated by an in vitro chromosomal aberration assay using Chinese hamster lung fibroblast cells (CHL/IU). Six of nine chemicals induced chromosomal aberrations; bromodichloromethane, chlorendic acid and isophorone induced structural aberrations, and chlorodibromomethane, pentachloroethane and 1,1,1,2-tetrachloroethane induced numerical aberrations (polyploidy). These six chemicals, therefore, are not uniquely positive in the MLA. The difference between the NTP results and ours might be due to the use of different cell lines and protocols, and in some cases, to different interpretations of polyploidy. The remaining three chemicals, benzyl acetate, cinnamyl anthranilate and trichloroethylene, were negative in this study.

Animals↗
PubMed1996

Truncation at conserved terminal regions of BRCA1 protein is associated with highly proliferating hereditary breast cancers.

The existence of two subgroups of BRCA1-associated breast cancer (BC) families has been recently posited: the first with highly proliferating tumors, and the second composed of cases with a low proliferation rate. Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the site of the germ line mutation in the BRCA1 gene. We analyzed the distribution of the mitotic index, a histoprognostic grade component shown to segregate in families, matching for germ line mutation location in a series of 28 breast cancers from 20 kindreds. We observed a prevalence of highly proliferating tumors when the mutation occurs in the two terminal conserved domains of the BRCA1 protein, ie., in the amino and carboxyl termini (P = 0.0024). Our data provide evidence for a genotype-phenotype correlation and along with their strong conservation during evolution argue for the importance of these two regions in the control of mammary cell growth.

Alleles↗
PubMed1996

Location of the non-heme iron center on the alpha subunit of photoreactive nitrile hydratase from Rhodococcus sp. N-771.

Nitrile hydratase (NHase) from Rhodococcus sp. N-771, which possesses a non-heme iron center binding nitric oxide (NO), is activated by light irradiation. To localize the iron center in the protein, we quantified Fe atoms and performed FTIR measurements of the isolated alpha and beta subunits. The native NHase and the isolated alpha subunit contained about 1.0 and 0.8 mol Fe per mol protein, respectively, whereas the beta subunit contained only a trace of Fe. An NO stretching band was observed at 1852 cm-1 in the FTIR spectrum of the alpha subunit, but not in that of the beta subunit. Upon light irradiation of the alpha subunit, the affinity of the Fe atom decreased and the NO band disappeared from the FTIR spectrum. These observations indicate that the non-heme iron center, which is responsible for the photoreaction, is present in the alpha subunit.

Amino Acid Sequence↗
PubMed1996

Integrated map of the chromosome 8p12-p21 region, a region involved in human cancers and Werner syndrome.

Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying the structure and function of the genome. To improve the definition of the 8p12-p21 chromosomal region, an integrated physical and genetic map was constructed extending from the genes. NEFL to FGFR1. The map comprises a series of contigs (the larger of these being around 9 Mb) of yeast artificial chromosomes (YACs) spanning the proximal region of deletion involved in a broad range of human cancers, including breast carcinomas, and in the Werner syndrome. In addition, losses of heterozygosity at 8p markers and linkage analysis of breast cancer families were also detailed. Finally, several genes potentially involved in 8p-associated diseases, namely GTF2E2, PPP2CB, and HGL, were precisely mapped within the YAC contigs. The reported map and contigs of YACs should facilitate the search for putative genes involved in sporadic and familial breast cancer as well as in the Werner syndrome.

Base Sequence↗
PubMed1996

Insulin- and polyunsaturated fatty acid-responsive region(s) of rat ATP citrate lyase gene promoter.

To investigate the regulatory DNA sequences required for insulin-stimulation of the ATP citrate-lyase (ACL) gene as well as for polyunsaturated fatty acid (PUFA)-suppression of this gene, primary cultured hepatocytes were transfected with plasmids containing the 5'-flanking sequence of the rat ACL gene fused to the chloramphenicol acetyltransferase (CAT) gene. Sequences from -861, -194 or -104 to +128 of the ACl gene directed an increase in CAT activity in hepatocytes when insulin was added to the medium containing either glucose or pyruvate. The CAT activities stimulated by insulin were reduced by the addition of PUFA, in accordance with the responses on the endogenous ACL gene expression. Further deletion to -20, however, resulted in loss of the responses. The results suggest that the region from -104 to -20 of the ACL gene is responsible for regulation due to insulin and PUFAs. In particular, the region from -61 to -49 of the ACL has sequence similarity to the insulin-responsive regions of fatty acid synthase and acetyl-CoA carboxylase.

ATP Citrate (pro-S)-Lyase↗
PubMed1996

Disordered expression of hepatic glycolytic and gluconeogenic enzymes in Otsuka Long-Evans Tokushima fatty rats with spontanteous long-term hyperglycemia.

Expression of key regulatory enzymes involved in glucose metabolism was studied in the livers of Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin dependent diabetes mellitus. The activity and mRNA levels of glucokinase and L-type pyruvate kinase was increased in the liver of OLETF rats compared with control rats. There was no such remarkable change in liver-type phosphofructokinase. The activities of glucose-6-phosphatase and fructose-1,6-biphosphatase also increase despite high plasma levels of glucose and insulin. The activity of phosphoenolpyruvate carboxykinase did not show any significant change. The mRNA levels for fructose-1,6-biphosphatase, and phosphoenolpyruvate carboxykinase exhibited no marked changes. These results suggest that the expression of glucose-6-phosphatase and fructose-1,6-biphosphatase is disordered in OLETF rats.

Animals↗
PubMed1996

Germ line mutation at BRCA1 affects the histoprognostic grade in hereditary breast cancer.

Histoprognostic grade is a determinant parameter to select the initial therapeutic strategy in breast cancer. Our aim was to analyze the grade repartition in BRCA1-associated breast cancer (BC) and to explore the possible connections between grade and the BRCA1 gene function. We first compared 27 BRCA1-associated BCs from 14 families with 4,461 cases from an administrative district registry and 242 cases from a hospital-based registry, matching for grade and constitutive elements, and then considered their repartition in families. We observed a prevalence of grade 3 (P < 0.0001) in BRCA1-associated BC. This was attributed mainly to nuclear polymorphism (P < 0.0001), mitotic activity (P < 0.0001), and tubular differentiation (P = 0.0004), implying that BRCA1-associated BCs are highly proliferating tumors. Moreover, it is suggested that grade segregates as a genetic trait within families (P = 0.0015), and this was attributed to the mitotic index segregation only (P = 0.0005). Therefore grade, through its components, could be interpreted as the morphological translation of the BRCA1 germ line mutation. Thus, a genotype-phenotype correlation may exist between the type of mutation and the aggressiveness of the disease. These findings are bound to have an important impact in the care management of hereditary breast cancer at the individual and at the familial level and in the comprehensive approach of breast cancer development.

Adult↗
PubMed1996

Alternative splicing of the pyruvate kinase M gene in a minigene system.

The M1-type and M2-type isozymes of pyruvate kinase are produced from a single gene by mutually exclusive use of exons 9 and 10. Selection of exon 10 generates the M2 type, which occurs in most tissues, whereas the M1 type is expressed by use of exon 9 only in skeletal muscle, heart and brain. We investigated the mechanism by which exon 10, but not exon 9 is selected in M2-expressing cells by transfecting minigenes containing exon 9 and/or exon 10 in cells and by analyzing the transcripts using reverse-transcriptase polymerase chain reaction. Deletion of the most conserved region in intron 8 did not affect selection of exon 10 in dRLh-84 cells, which express only the M2 type. Exclusion of exon 10 from the minigene resulted in two major spliced products. One included correctly spliced exon 9 and the other skipped this exon. Similar splicing patterns were observed when these minigenes were transfected in hepatocytes which express the L type, but not M1 or M2 types. The 5' splice site but not the 3' splice site of exon 9 was found to be hardly recognized by the splicing machinery in dRLh-84 cells. Mutation of the 5' splice site sequence of exon 9 to that of exon 10 and vice versa did not change the splicing patterns. However, mutation of this site of exon 9 to a perfectly complementary sequence of U1 snRNA resulted in selection of exon 9 correctly spliced to exon 10. A 9-10 fusion exon (constructed by substitution of 68 bases of the 3' portion of exon 9 and 33 bases of the 5' portion of intron 9 for the corresponding regions of exon 10 and intron 10) was also correctly incorporated into a major product together with exon 10. Thus, we propose that exon 9 is not recognized in non M1-expressing cells due to the weak signal of its 5' splice site and that, although the 5' splicing signal of exon 10 also appears to be weak, this exon can be recognized in these cells because the 5' recognition signal may be relatively strengthened by cis-acting element(s) which may be present in the 3' portion of exon 9 and the 5' portion of intron 9 and/or the corresponding regions of exon 10 and intron 10.

Alternative Splicing↗