Search PubMed⌕ Search

Biomedical subjects

N Nitta

Publications and source records attributed to N Nitta.

At least 37 records · Page 2Linked to original sources
PubMed1988

Is the deterioration of liver viability due to hepatic warm ischemia or reinflow of pooled-portal blood in intermittent portal triad cross-clamping?

The effects of hepatic warm ischemia and portal pooling on the viability of the liver were investigated with respect to hepatic energy metabolism by performing intermittent portal triad cross-clamping (Pringle's maneuver) on dogs with or without portosystemic shunt. The dogs were divided into two groups of five: Group 1, non-shunt group, underwent Pringle's maneuver performed for 30 min and declamping for 30 min, a process that was repeated five times; and Group 2, shunt group, underwent the same procedure as Group 1, except for portosystemic shunt using a heparinized hydrophilic catheter between the splenic and jugular veins. The shunt was opened during Pringle's maneuver and was closed immediately at declamping. In the non-shunt group, portal pooling increased and systemic blood pressure decreased when Pringle's maneuver was performed, but in the shunt group portal and systemic blood pressures remained within the normal range. In the non-shunt group, the initial velocity of arterial blood ketone body ratio (KBR) recovery after each declamping significantly (P less than 0.01) decreased from 0.122 +/- 0.016 (per min) after the first declamping to 0.028 +/- 0.017 (per min) after the fifth declamping. Hepatic energy charge [= (ATP + 1/2 ADP)/(ATP + ADP + AMP)] decreased from 0.840 +/- 0.003 before ischemia to 0.749 +/- 0.003 30 min after the fifth declamping (P less than 0.001). The concentrations of lactate and total amino acids in arterial blood increased. On the other hand, in the shunt group, the initial velocity of KBR recovery and hepatic energy charge showed little change even after the fifth declamping (0.081 +/- 0.016 per min and 0.851 +/- 0.009, respectively). The concentrations of lactate and total amino acids showed almost no increase. The impairment of hepatic energy metabolism by intermittent portal triad cross-clamping is mainly due to reinflow of pooled-portal blood to the previously ischemic liver, rather than hepatic warm ischemia. The KBR may be useful for determining the degree of impairment of hepatic energy metabolism.

Amino Acids↗
PubMed1988

Arterial blood ketone body ratio as an indicator of the no-return point in hepatic inflow occlusion without venous shunt in dogs.

The effects of hepatic inflow occlusion without venous shunt on the viability of the liver were investigated with respect to liver energy metabolism in dogs, subjected to portal triad cross-clamping (Pringle's maneuver) for 10, 30 and 60 min. The concentrations of ketone bodies and the arterial blood ketone body ratio (KBR) were decreased markedly by hepatic inflow occlusion, but recovered upon recirculation. The initial velocity of KBR recovery was 0.150/min after 10-min clamping, 0.140/min after 30-min clamping and 0.032/min after 60-min clamping. KBR recovery was delayed when hepatic inflow occlusion exceeded 30 min, which indicates that hepatic inflow occlusion for 60 min causes severe inhibition of energy generation in liver mitochondria. These findings indicate that the safety period for hepatic inflow occlusion without venous shunt is between 30 and 60 min in dogs, and that mortality can be predicted by measuring the initial velocity of KBR recovery upon recirculation.

Animals↗
PubMed1988

Changes in concentrations of respiratory components and cytochrome oxidase activity in mitochondria obtained from carbon tetrachloride-induced cirrhotic rat liver.

1. Changes in the concentrations of respiratory components, phosphorylative activity, the cytochrome oxidase activity of mitochondria and the hepatic adenylate energy charge level (in situ) were studied in cirrhotic rat liver induced by carbon tetrachloride (CCl4). 2. In the cirrhotic liver mitochondria, concentrations of cytochrome a(+a3), cytochrome b, coenzyme Q9 and coenzyme Q10 increased significantly to 2.44 +/- 0.02 x 10(-10) (mean +/- SE), 1.37 +/- 0.05 x 10(-10), 25.57 +/- 0.47 x 10(-10) and 5.39 +/- 0.26 x 10(-10) mol/mg of mitochondrial protein, respectively, compared with 1.83 +/- 0.03 x 10(-10), 1.22 +/- 0.02 x 10(-10), 16.24 +/- 0.39 x 10(-10) and 1.81 +/- 0.07 x 10(-10) in normal rats [P less than 0.001 for cytochrome a(+a3), coenzyme Q9 and coenzyme Q10, and P less than 0.01 for cytochrome b]. 3. Concentrations of flavoprotein and pyridine nucleotides decreased significantly to 13.33 +/- 0.14 x 10(-10) and 45.68 +/- 1.59 x 10(-10) mol/mg of mitochondrial protein, respectively, compared with 14.79 +/- 0.33 x 10(-10) and 86.26 +/- 1.83 x 10(-10) in normal rats (P less than 0.001). There was no significant difference in the concentration of cytochrome c(+c1). 4. Cytochrome oxidase activity per unit of cytochrome a(+a3) increased significantly to 67.43 +/- 1.71 atoms O s-1 mol-1, compared with 55.77 +/- 1.16 in normal rats (P less than 0.001). By contrast, phosphorylative activity per unit of cytochrome a(+a3) decreased significantly in the cirrhotic liver to 10.40 +/- 0.36 s-1 compared with 13.43 +/- 0.49 in normal rats (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1988

Changes in energy metabolism of allografts after liver transplantation.

To evaluate the function of energy metabolism in allografts after liver transplantation, changes in hepatic energy charge levels, oxidative and phosphorylative activities of mitochondria and arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate; KBR) were studied in piglets. Hepatic energy charge levels decreased to 0.831 +/- 0.010 at 3 days and 0.836 +/- 0.009 at 3 weeks after operation compared to the preoperative value of 0.868 +/- 0.006 (p less than 0.01), and returned to 0.856 +/- 0.007 at 6 weeks. Mitochondrial oxidative and phosphorylative activities were moderately enhanced to 19.14 +/- 2.07 (10(-10) mol ATP/mg of mitochondrial protein/s) at 3 days and 20.89 +/- 1.72 at 3 weeks compared to the preoperative value of 16.74 +/- 2.36, and returned to 16.65 +/- 1.54 at 6 weeks. There was no significant difference in the concentrations of mitochondrial respiratory components, except in cytochrome c + c1. KBR decreased immediately at the beginning of the anhepatic phase and rapidly recovered to the preoperative level within 60 min after revascularization of allografts. There was no change in KBR during the postoperative course except in cases with clinical deterioration. From these results, it is suggested that the mitochondrial capacity for ATP synthesis was enhanced to compensate for the decreased energy charge level and that a decreased KBR is a sign of a critically deranged metabolic function in allografts.

Adenosine Triphosphate↗
PubMed1988

Deleterious effects of splanchnic congestion on hepatic energy metabolism following repeated portal triad cross-clamping in dogs.

Thirty minutes of warm hepatic ischemia produced by portal triad cross-clamping was repeated five times at 30-minute intervals in three groups of five dogs each: Group A was subjected only to portal triad cross-clamping; Group B received simultaneous clamping of the celiac axis and the superior mesenteric artery; and Group C had a simultaneous splenojugular shunt. The arterial blood ketone body ratio (acetoacetate/beta-hydroxybutyrate: KBR), reflecting the NAD+/NADH ratio in liver mitochondria, decreased significantly after each cross-clamping in all groups. After the first declamping, there was no significant difference in the recovery rate of the KBR among the three groups. After the second declamping, the recovery rate in Group A decreased significantly compared with the rates of Groups B and C (P less than 0.05). After the fourth declamping, the recovery rate in Group B was significantly lower than that of Group C (P less than 0.05). The hepatic energy charge [(ATP + 1/2ADP)/(ATP + ADP + AMP)] 30 minutes after the fifth declamping decreased significantly to 0.75 +/- 0.01 in Group A, compared with 0.84 +/- 0.01 in Group C (P less than 0.01). The lactate and total free plasma amino acid levels in the arterial blood increased significantly in the order of Groups A, B, and C. It is suggested that the inflow of stagnant portal venous blood to ischemic liver impairs hepatic energy metabolism.

Amino Acids↗
PubMed1987

Short-term changes in blood ketone body ratio in the phase immediately after liver transplantation.

Arterial blood ketone body ratio was measured after orthotopic liver transplantation in piglets. Ketone body ratio immediately decreased at the beginning of the anhepatic phase and was rapidly restored to the normal levels within 30 min after the revascularization of the allograft. Serum lactate and pyruvate levels increased in anhepatic phase and gradually decreased after revascularization. Changes in the lactate and pyruvate levels were always preceded by changes in ketone body ratio. In the case of transplantation after 12-hr-preservation of the allograft, ketone body ratio failed to maintain normal levels after transplantation, resulting in a high mortality. It is suggested that the elevation of decreased ketone body ratio is prerequisite for the normalization of the deranged metabolic state after liver transplantation, and that ketone body ratio provides an accurate means to assess the initial metabolic function of the allograft.

Animals↗
PubMed1987

Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient.

The activation of proto-oncogenes in colorectal cancers in Japanese patients was studied using a mouse NIH3T3 cell transfection assay system. Of thirty-five colorectal cancers examined, one rectal cancer showed an unusually high transformation efficiency and, in this rectal cancer, the N-ras oncogene was found to be activated. Nucleotide sequence analysis of the activated N-ras showed a single G----C point mutation at the first letter of codon 13, resulting in the coding of arginine instead of glycine. This amino-acid substitution at codon 13 may be responsible for the efficient induction of transformants of NIH3T3 cells in vitro.

Animals↗
PubMed1986

Cross-linking between 16S ribosomal RNA and protein S4 in Escherichia coli ribosomal 30S subunits effected by treatment with bisulfite/hydrazine and bromopyruvate.

Cytosine in nucleic acids can be modified by treatment with a mixture of bisulfite and hydrazine. The reaction is specific for single-stranded regions of nucleic acids and the product is N4-aminocytosine. Bromopyruvate has been used for alkylation of protein SH groups and through its 2-oxo group it can form a hydrazone with N4-aminocytosine. Escherichia coli ribosomal 30S subunits were treated with 1 M sodium bisulfite + 2 M hydrazine in the presence of 10 mM MgCl2 at pH 7.0 and 37 degrees C for 30 min. By this treatment, 2.4 cytosine residues/molecule 16S rRNA were derivatized into N4-aminocytosines. 35S-labeled 30S subunits were modified in this way and then treated with 10 mM bromopyruvate at pH 8.0 and 37 degrees C for 5 min. Analysis in sodium dodecyl sulfate/sucrose density gradient centrifugation showed co-sedimentation of a part of the 35S radioactivity with the RNA. The co-sedimentation was dependent on both the bisulfite/hydrazine and the bromopyruvate treatments. The RNA-protein complex was prepared from unlabeled 30S subunits. The protein portion was labeled with 125I, the RNA portion was digested with nucleases, and then the hydrazone linkage between the protein and oligonucleotides was cleaved by treatment with 0.2 M HCl. The oligonucleotides formed were removed by dialysis and the protein was identified as S4 by two-dimensional electrophoresis and by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The results indicate that the cysteinyl residue of protein S4 at position 31 from the N-terminus is located close to a cytosine residue which is non-base-paired and easily accessible by the externally present bisulfite/hydrazine reagent.

Electrophoresis, Polyacrylamide Gel↗
PubMed1984

A new reaction useful for chemical cross-linking between nucleic acids and proteins.

Cytosine in nucleic acids can be converted into N4-aminocytosine by treatment with a mixture of hydrazine and bisulfite. The hydrazino group thus formed at position 4 of the pyrimidine ring can be linked to a sulhydryl group in proteins by the use of bromopyruvate as a linker. Successful use of this scheme of chemical cross-linking between nucleic acid and protein was demonstrated in the linking of poly(C) with glutathione, and of RNA with protein in the E. coli 30 S ribosomal subunit.

Cross-Linking Reagents↗
PubMed1984

Role of prostaglandin E2 in contractile abnormality induced by calcium ionophore, A23187.

We evaluated the possible role of prostaglandin E2 (PGE2) in the calcium(Ca++)-mediated damage of skeletal muscle by a calcium ionophore (A23187) that induces excessive Ca++ influx. Twitch and tetanus of rat diaphragms were depressed with either PGE2 or A23187. A23187-induced depression was reduced by PG synthesis inhibitors, aspirin, or indomethacin, though less than that by a protease inhibitor, leupeptin. PGE2-induced depression was also inhibited by leupeptin. Damage of the muscle cell by excessive intracellular free Ca++ may thus be mediated via a PGE2 pathway besides other mechanisms including non-lysosomal, Ca++-activated proteases.

Animals↗
PubMed1983

N4-aminocytidine, a nucleoside analog that has an exceptionally high mutagenic activity.

The reaction of cytidine with hydrazine to give N4-aminocytidine was greatly promoted by addition of a less-than-stoichiometric amount of bisulfite, and the product was isolated in a good yield. N4-Aminocytidine was strongly mutagenic to bacteria (Salmonella typhimurium TA100 and TA1535, and E. coli WP2 uvrA) and to phage (phi X174 am3). The activity did not require the presence of mammalian microsomal fraction in the system. The mutagenic potency of N4-aminocytidine in these systems was two orders of magnitude greater than that of N4-amino-2'-deoxycytidine, and more than two orders of magnitude greater than that of N4-hydroxycytidine. The greater activity of the riboside than the deoxyriboside was ascribed to the lack of deoxycytidine kinase in these cells. This compound may be useful as a powerful mutagen to induce a transition mutation in microorganisms.

Bacteriophage phi X 174↗