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H Nishida

Publications and source records attributed to H Nishida.

At least 55 records · Page 3Linked to original sources
PubMed2001

Evolution of amino acid biosynthesis and enzymes with broad substrate specificity.

UNLABELLED: I selected 82 proteins that were related to amino acid biosynthesis in the genome of Escherichia coli. I then searched the extensive sequence homology for each of the selected proteins from among the proteins of E.coli. The result showed that 30 proteins of the selected proteins had extensive sequence homology within the selected proteins, and 21 proteins had extensive sequence homology to proteins outside the selected proteins. In addition, the enzymes with broad substrate specificity play an important role in the amino acid biosynthesis. I demonstrate here that some substrate-specific enzymes evolved from an ancestor enzyme with broad substrate specificity. CONTACT: hnishida@iam.u-tokyo.ac.jp

Amino Acids↗
PubMed2001

Distribution of genes for lysine biosynthesis through the aminoadipate pathway among prokaryotic genomes.

Deinococcus radioduranshas homologous genes to the genes which from the Thermus: thermophilus gene cluster for lysine biosynthesis. Interestingly, those genes are clustered in Thermus, nevertheless they are scattered in Deinococcus. A similar gene cluster has only been found in Pyrococcus However, the phylogenetic analyses indicated that the deduced gene products from Deinococcus were the most closely related to the proteins encoded in the Thermus gene cluster for lysine biosynthesis. Therefore, those genes had not been transferred horizontally between Pyrococcus and Thermus. It is strongly suggested that a common ancestor of Deinococcus and Thermus possessed the genes for lysine biosynthesis through the aminoadipate pathway. These had been clustered through the evolution of Thermus or had been scattered from the gene cluster through the evolution of Deinococcus. In addition, I showed that LysW and its homologues were specialized proteins for the prokaryotic lysine biosynthesis through the aminoadipate pathway.

Amino Acid Sequence↗
PubMed2001

Effects of flavin-binding motif amino acid mutations in the NADH-cytochrome b5 reductase catalytic domain on protein stability and catalysis.

Porcine NADH-cytochrome b5 reductase catalytic domain (Pb5R) has the RXY(T/S)+(T/S) flavin-binding motif that is highly conserved among the structurally related family of flavoprotein reductases. Mutations were introduced that alter the Arg(63), Tyr(65), and Ser(99) residues within this motif. The mutation of Tyr(65) to either alanine or phenylalanine destabilized the protein, produced an accelerated release of FAD in the presence of 1.5 M guanidine hydrochloride, and decreased the k(cat) values of the enzyme. These results indicate that Tyr(65) contributes to the stability of the protein and is important in the electron transfer from NADH to FAD. The mutation of Ser(99) to either alanine or valine, and of Arg(63) to either alanine or glutamine increased both the K(m) values for NADH (K(m)(NADH)) and the dissociation constant for NAD(+) (K(d)(NAD+)). However, the mutation of Ser(99) to threonine and of Arg(63) to lysine had very little effect on the K(m)(NADH) and K(d)(NAD+) values, and resulted in small changes in the absorption and circular dichroism spectra. These results suggest that the hydroxyl group of Ser(99) and the positive charge of Arg(63) contribute to the maintenance of the properties of FAD and to the effective binding of Pb5R to both NADH and NAD(+). In addition, the mutation of Arg(63) to either alanine or glutamine increased the apparent K(m) values for porcine cytochrome b5 (Pb5), while changing Arg(63) to lysine did not. The positive charge of Arg(63) may regulate the electron transfer through the electrostatic interaction with Pb5. These results substantiate the important role of the flavin-binding motif in Pb5R.

Amino Acid Motifs↗
PubMed2001

Effects of different durations of exercise on macrophage functions in mice.

The effects of differing durations of daily exercise on macrophage functions in mice were studied. Male ICR mice aged 4 wk were divided into five groups: a nonexercise group (control) and four exercise groups with differing daily exercise durations of 15--120 min (Exr groups). The exercise applied was 5 days/wk treadmill running at 13 m/min for 12 wk. The potentiation of the phagocytosis function of the reticuloendothelial system and the glucose consumption of peritoneal macrophages in the Exr 30, 60, and 120 groups were significantly higher than those in the control group. Superoxide anion production of peritoneal macrophages in both the absence and the presence of phorbol 12-myristate 13-acetate in the Exr 60 and 120 groups was significantly higher than that in the control group. The acid phosphatase and beta-glucuronidase activities of peritoneal macrophages in the Exr 30, 60, and 120 groups were significantly increased. These results suggest that treadmill running exercise for at least 30 min/day (30--120 min) effectively enhances macrophage functions in mice. These data provide preliminary evidence indicating that chronic exercise-induced increases in phagocytic activity exhibit a dose-dependent relationship with exercise duration.

Acid Phosphatase↗
PubMed2001

Binary specification of nerve cord and notochord cell fates in ascidian embryos.

In the ascidian embryo, the nerve cord and notochord of the tail of tadpole larvae originate from the precursor blastomeres for both tissues in the 32-cell-stage embryo. Each fate is separated into two daughter blastomeres at the next cleavage. We have examined mechanisms that are responsible for nerve cord and notochord specification through experiments involving blastomere isolation, cell dissociation, and treatment with basic fibroblast growth factor (bFGF) and inhibitors for the mitogen-activated protein kinase (MAPK) cascade. It has been shown that inductive cell interaction at the 32-cell stage is required for notochord formation. Our results show that the nerve cord fate is determined autonomously without any cell interaction. Presumptive notochord blastomeres also assume a nerve cord fate when they are isolated before induction is completed. By contrast, not only presumptive notochord blastomeres but also presumptive nerve cord blastomeres forsake their default nerve cord fate and choose the notochord fate when they are treated with bFGF. When the FGF-Ras-MAPK signaling cascade is inhibited, both blastomeres choose the default nerve cord pathway, supporting the results of blastomere isolation. Thus, binary choice of alternative fates and asymmetric division are involved in this nerve cord/notochord fate determination system, mediated by FGF signaling.

Animals↗
PubMed2001

Large-scale cDNA analysis of the maternal genetic information in the egg of Halocynthia roretzi for a gene expression catalog of ascidian development.

The ascidian egg is a well-known mosaic egg. In order to investigate the molecular nature of the maternal genetic information stored in the egg, we have prepared cDNAs from the mRNAs in the fertilized eggs of the ascidian, Halocynthia roretzi. The cDNAs of the ascidian embryo were sequenced, and the localization of individual mRNA was examined in staged embryos by whole-mount in situ hybridization. The data obtained were stored in the database MAGEST (http://www.genome.ad.jp/magest) and further analyzed. A total of 4240 cDNA clones were found to represent 2221 gene transcripts, including at least 934 different protein-coding sequences. The mRNA population of the egg consisted of a low prevalence, high complexity sequence set. The majority of the clones were of the rare sequence class, and of these, 42% of the clones showed significant matches with known peptides, mainly consisting of proteins with housekeeping functions such as metabolism and cell division. In addition, we found cDNAs encoding components involved in different signal transduction pathways and cDNAs encoding nucleotide-binding proteins. Large-scale analyses of the distribution of the RNA corresponding to each cDNA in the eight-cell, 110-cell and early tailbud embryos were simultaneously carried out. These analyses revealed that a small fraction of the maternal RNAs were localized in the eight-cell embryo, and that 7.9% of the clones were exclusively maternal, while 40.6% of the maternal clones showed expression in the later stages. This study provides global insights about the genes expressed during early development.

Animals↗
PubMed2001

The BMP signaling pathway is required together with the FGF pathway for notochord induction in the ascidian embryo.

The 40 notochord cells of the ascidian tadpole invariably arise from two different lineages: the primary (A-line) and the secondary (B-line) lineages. It has been shown that the primary notochord cells are induced by presumptive endoderm blastomeres between the 24-cell and the 64-cell stage. Signaling through the fibroblast growth factor (FGF) pathway is required for this induction. We have investigated the role of the bone morphogenetic protein (BMP) pathway in ascidian notochord formation. HrBMPb (the ascidian BMP2/4 homologue) is expressed in the anterior endoderm at the 44-cell stage before the completion of notochord induction. The BMP antagonist Hrchordin is expressed in a complementary manner in all surrounding blastomeres and appears to be a positive target of the BMP pathway. Unexpectedly, chordin overexpression reduced formation of both primary and secondary notochord. Conversely, primary notochord precursors isolated prior to induction formed notochord in presence of BMP-4 protein. While bFGF protein had a similar activity, notochord precursors showed a different time window of competence to respond to BMP-4 and bFGF. Our data are consistent with bFGF acting from the 24-cell stage, while BMP-4 acts during the 44-cell stage. However, active FGF signaling was also required for induction by BMP-4. In the secondary lineage, notochord specification also required two inducing signals: an FGF signal from anterior and posterior endoderm from the 24-cell stage and a BMP signal from anterior endoderm during the 44-cell stage.

Animals↗
PubMed2001

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitor.

Intravascular clot formation is an important factor in a number of cardiovascular diseases. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), which is a key enzyme in coagulation cascade responsible for the generation of thrombin by limited proteolysis of its zymogen, prothrombin. We have investigated 1-arylsulfonyl-3-piperazinone derivatives, containing a 4-(piperidino)pyridine group in place of guanidino and/or amidino groups, and discovered compound M55113 (30a: 4-[(6-Chloro-2-naphthalenyl)sulfonyl]-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]piperazinone), as a potent inhibitor of FXa (IC50=0.06 microM) with high selectivity for FXa over trypsin and thrombin.

Anticoagulants↗
PubMed2001

Off-pump reimplantation of anomalous origin of the right coronary artery.

A 30-year-old man was diagnosed to have an anomalous origin of the right coronary from the pulmonary artery. Through a mini-sternotomy, without extracorporeal circulation, reimplantation of the anomalous origin of the right coronary artery from the pulmonary artery to the aorta was successfully performed. This is a successful case of off-pump cardiac correction of this type of isolated anomaly, using a minimally invasive approach.

Adult↗
PubMed2001

Audiological findings in patients with myoclonic epilepsy associated with ragged-red fibres.

Sensorineural hearing loss is a common symptom in patients with myoclonic epilepsy associated with ragged-red fibres (MERRF), one of the mitochondrial encephalomyopathies, although the lesion causing hearing loss in such cases remains unknown. Here we describe the audiological features in three MERRF patients, all of whom exhibited a point mutation in their mitochondrial DNA at nucleotide 8344. Pure-tone threshold audiometry revealed bilateral, sloping-type, sensorineural hearing loss in all three patients. Distortion product otoacoustic emissions, electrocochleography, and auditory brainstem responses were variable, even differing between the right and left ears of the same patient. Taken together, our findings suggest that the primary lesion underlying hearing loss in MERRF patients is in the cochlea, although a retrocochlear lesion may be involved in some patients.

Adolescent↗
PubMed2001

CJ-13,981 and CJ-13,982, new squalene synthase inhibitors.

Two new squalene synthase (SSase) inhibitors, CJ-13,981 (I) and CJ-13,982 (II), were isolated from the fermentation broth of an unidentified fungus CL 15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 microM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 microM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3,4-dicarboxy-15-hexadecenoic acid and 3-hydroxy-3,4-dicarboxyhexadecanoic acid, respectively.

Alkyl and Aryl Transferases↗
PubMed2001

CJ-19,784, a new antifungal agent from a fungus, Acanthostigmella sp.

A new antifungal agent, CJ-19,784 (I), was isolated from the fermentation broth of a fungus, Acanthostigmella sp. CL12082. Based on spectroscopic analyses, structure of I was determined to be 3'-bromo-2',5-dihydroxy-3,7,8-trimethoxy-flavone. Compound I inhibits the growth of pathogenic fungi, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus with IC50 values of 0.11, 20 and 0.54 microg/ml, respectively.

Antifungal Agents↗
PubMed2001

Cytokine production inhibitors produced by a fungus, Oidiodendron griseum.

A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271alpha, LL-Z1271gamma, CJ-14,445, PR 1388, CJ-14,604 and a new diterpene, CJ-14,515. They inhibited both lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production in human whole blood with IC50s of the range from 0.049 to 100 microM.

Ascomycota↗
PubMed2001

Novel cytokine production inhibitors produced by a basidiomycete, Marasmiellus sp.

New cytokine production inhibitors, CJ-14,877 (I) and CJ-14,897 (II), were isolated from the fermentation broth of a basidiomycete, Marasmiellus sp. CL21624. Their structures were determined to be methyl-(7S,8S)-5-(7,8-dihydroxypropyl)pyridine-2-carboxylate and methyl-(7S,8S)-5-(8-acetoxy-7-hydroxypropyl)pyridine-2-carboxylate [corrected], respectively, by spectroscopic analyses. These compounds showed inhibitory activities for lipopolysaccharide-induced production of interleukin-1beta and tumor necrosis factor-alpha in human whole blood with IC50 values of the range from 0.059 to 2.6 microM.

Agaricales↗
PubMed2001

CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus aculeatus.

A new squalene synthase (SSase) inhibitor, CJ-15,183 (I) was isolated from the fermentation broth of a fungus, Aspergillus aculeatus CL38916. The compound potently inhibited rat liver and Candida albicans microsomal SSases and also inhibited the human enzyme. It also showed antifungal activities against filamentous fungi and a yeast. The structure was determined to be an aliphatic tetracarboxylic acid compound consisting of an alkyl gamma-lactone, malic acid and isocitric acid moieties by spectroscopic studies.

Alkenes↗
PubMed2001

Coronary artery bypass grafting in 105 patients with hemodialysis-dependent renal failure.

This study was proposed to define early and long-term results of coronary artery bypass grafting (CABG) in dialysis-dependent renal failure (RF) patients, and preoperative patient characteristics. This study included 105 patients (87 males and 18 females; mean age 60.0 +/- 9.0 years, range 39-79) with RF on maintenance dialysis (hemodialysis 100, peritoneal dialysis 5) who underwent isolated CABG between August 1985 and April 2000. Postoperative follow-up was completed in 100% and averaged 3.1 years. There were 22 emergency and 2 re-CABG cases. Previous myocardial infarction (MI) was found in 55 patients (52%), and unstable angina was noted in 53 patients (50%). Diabetes mellitus was the cause of RF in 50 patients (48%; 24 patients required insulin). There was 1 case of single vessel disease, 31 cases of double vessel disease, 54 cases of triple vessel disease, and 19 cases of left main disease. Preoperative left ventriculography was performed in 92 patients (88%). Left ventricular ejection fraction (LVEF) was 48.3 +/- 15.8% (range 11-74%) and was 40% or less in 25 patients (27%). The mean number of distal anastomoses was 2.5 (range 1-5). Three patients received only vein grafts, but all were cases of emergency CABG. The remaining 102 patients (97%) received at least 1 arterial conduit. Among them, 64 patients received only arterial conduits, and 72 patients received 2 or more distal anastomoses with arterial conduits. Five patients (4.8%) died within 30 days after CABG (2 cardiac deaths and 3 noncardiac deaths), and 8 patients (7.6%) died beyond 30 days after CABG before discharge (all noncardiac deaths). The cause of 2 cardiac deaths was abrupt circulatory collapse during or after hemodialysis in patients with severe left ventricular dysfunction (LVEF; 11% and 28%) in the early postoperative period. The causes of 8 noncardiac deaths included infection in 4 and rupture of aortic aneurysm, stroke, sleep apnea syndrome, and mesenteric infarction. During the follow-up period, there were 29 late deaths (8 cardiac, 13 noncardiac, and 8 sudden death), 6 MIs, 13 percutaneous transluminal coronary angioplasty, and 1 re-CABG. The 5-year actuarial survival rate was 59.8%, the cardiac death-free rate was 83.0%, and the cardiac event-free rate was 62.4%. Although CABG in patients on hemodialysis is associated with high early and long-term mortality in terms of both cardiac and noncardiac deaths in proportion to the severity of the preoperative condition, long-term survival was still better than that of general dialysis patients. Meticulous perioperative management may be the key factor in the improvement of early results.

Adult↗