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Biomedical subjects

T Nonaka

Publications and source records attributed to T Nonaka.

At least 109 records · Page 6Linked to original sources
PubMed1993

Alteration of hepatic enzyme activities in obese KK mice treated with monosodium aspartate.

Changes in body weight, concentrations of urine glucose, blood glucose, plasma insulin and FFA and hepatic enzyme activities were investigated in KK and C57BL mice treated with monosodium-L-aspartate (MSA). MSA was administered subcutaneously to neonates at a dose of 4 mg/g body weight. The MSA-treated KK and C57BL mice were remarkably obese at 10 weeks of age. The average plasma insulin concentration in the control KK mice was 73.6 microU/ml, over 4 times higher than in the control C57BL mice. In the control KK mice, hepatic glucokinase (GK) activity was quite low, and fructose-1,6-bisphosphatase (FBP) and acetyl-CoA carboxylase (CBX) activity was much higher than in the control C57BL mice. In the MSA-treated KK and C57BL mice, the plasma insulin concentration increased to 2 to 3 times higher than in the controls. The MSA-treated C57BL mice showed an increase in GK and CBX activity and acceleration of obesity. In the MSA-treated KK mice, GK activity did not change and CBX activity decreased, and only FBP activity increased significantly. Glycosuria was induced and blood glucose and plasma FFA increased remarkably in all MSA-treated KK mice.

Acetyl-CoA Carboxylase↗
PubMed1993

[Detection of minus strand HCV RNA in liver tissue by reverse transcriptase polymerase chain reaction (RT-PCR)].

Hepatitis C virus RNA in serum and liver tissue was examined in seven patients with liver cirrhosis by reverse transcriptase polymerase chain reaction method using primers for 5'-non-coding region. Plus strand HCV RNA were detected in serum and liver tissues in five of five patients who had HCV antibodies (C100-3 antibody and P22 antibody) and were not detected in two of two patients who do not have HCV antibody. Minus strand HCV RNA was detected in liver tissue of five HCV antibody positive patients. These results suggest that HCV are present and replicate in liver tissue in patients with liver cirrhosis.

Base Sequence↗
PubMed1992

Histamine-induced differentiation of HL-60 cells. The role of cAMP and protein kinase A.

When HL-60 cells were stimulated with histamine, a significant differentiation of the cells toward neutrophils was elicited. Histamine increased phagocytic activity, but it reduced myeloperoxidase activity of HL-60 cells. Histamine-induced differentiation in HL-60 cells was inhibited not only by H2 antagonists, such as cimetidine, ranitidine and famotidine, but also by an inhibitor of protein kinase A (A kinase), KT-5720. Histamine increased the cAMP level and A kinase activity in HL-60 cells; both increases preceded the cell differentiation. Histamine also enhanced phosphorylation of a 160 kD protein in HL-60 cells, while H2 antagonists and KT-5720 inhibited this phosphorylation. The results of the present study indicate that an activation of A kinase via H2 receptor stimulation may cause the phosphorylation of a 160 kD protein and that this phosphorylation is probably involved in the process leading to differentiation of HL-60 cells.

Carbazoles↗
PubMed1992

Analysis of binding protein for tissue-type plasminogen activator in human endothelial cells.

The specific binding sites for tissue-type plasminogen activator (t-PA) were investigated in human umbilical vein endothelial cells. After adding 125I-t-PA (M.W. 70 kDa) to endothelial cells in suspension culture, the ligand was recovered from the cell extract after disuccinimidyl suberate treatment as a high molecular complex with M.W. of 90 kDa on SDS-PAGE. The complex reacted to only anti-t-PA IgG but not to anti-PAI-1 IgG immunoblot analysis, indicating a t-PA specific binding protein. 125I-t-PA ligand blotting of the cell extract revealed that the binding protein had M.W. 20 kDa. The binding of 125I-t-PA to endothelial cells was reduced in the presence of an excess amount of t-PA, plasminogen and 6-aminohexanoic acid, indicating that the binding sites were also recognized by plasminogen, and that t-PA and plasminogen were bound via lysine binding sites in the molecule. These findings suggest that human endothelial cells have specific t-PA binding molecules which may be expressed on the cell surface as t-PA receptors.

Aminocaproic Acid↗
PubMed1992

Crystal structure of an engineered subtilisin inhibitor complexed with bovine trypsin.

Proteinase specificity of a proteinaceous inhibitor of subtilisin (SSI; Streptomyces subtilisin inhibitor) can be altered so as to strongly inhibit trypsin simply by replacing P1 methionine with lysine (with or without concomitant change of the P4 residue) through site-directed mutagenesis. Now the crystal structure of one such engineered SSI (P1 methionine converted to lysine and P4 methionine converted to glycine) complexed with bovine trypsin has been solved at 2.6 A resolution and refined to a crystallographic R factor of 0.173. Comparing this structure with the previously established structure of the native SSI complexed with subtilisin BPN', it was found that (i) P1 lysine of the mutant SSI is accommodated in the S1 pocket of trypsin as usual, and (ii) upon complex formation, considerable conformation change occurs to the reactive site loop of the mutant SSI. Thus, in this case, flexibility of the reactive site loop seems important for successfully changing the proteinase specificity through mere replacement of the P1 residue.

Amino Acid Sequence↗
PubMed1992

Analysis of K+ transport by rabbit CCD: conductive pathways and K(+)-K+ exchange by Na(+)-K+ pump.

We studied the cellular pathways of K+ transport by the rabbit cortical collecting duct that was stimulated to absorb Na+ and to secrete K+. The vast majority of K+ secretion (into the lumen) was inhibited by benzamil, a blocker of epithelial Na+ channels. The residual K+ secretion was completely inhibited by ouabain. Thus all active K+ secretion was dependent on Na+ transport by the Na(+)-K+ pump. The passive pathways of K+ transport were further examined using tracer and electrophysiological measurements. K+ transfer across the apical membrane was predominantly or exclusively conductive; the apical K+ conductance was 31 mS/cm2. The basolateral membrane contained two pathways for K+ tracer translocation. The (barium-sensitive) conductive pathway accounted for a relatively small (12-20%) portion of the tracer permeation. A larger pathway appeared to be via K(+)-K+ exchange on the Na(+)-K+ pump. The magnitude of the Ba2(+)-sensitive (basolateral) K+ conductance predicted a substantially larger tracer flux than was actually measured. The best explanation for this difference is the presence of single-file diffusion through K+ channels on the apical and basolateral membranes. An analysis of the electrically silent K+ transport from lumen to bath suggests that the Na(+)-K+ pump can vary the ratio of its Na(+)-K+ and K(+)-K+ modes of operation. When the tubule is actively transporting Na+ and K+, the Na(+)-K+/K(+)-K+ turnover ratio is greater than 7. When Na+ transport is limited by inhibiting Na+ entry across the apical membrane, the ratio falls to less than 1. A major factor determining this ratio is probably the availability of Na+ to the cytoplasmic side of the pump.

Animals↗
PubMed1992

Alterations in acetyl coenzyme A carboxylase activities in voles and mice treated with monosodium aspartate.

Changes of body weights and hepatic acetyl-CoA carboxylase activities were measured in voles and mice treated with monosodium-L-aspartate (MSA). MSA was administrated subcutaneously to neonates at 4 mg/g. The MSA-treated mice showed remarkable obesity, associated with the increase in the plasma insulin concentrations and acetyl-CoA carboxylase activities. The activity of acetyl-CoA carboxylase of control voles was very low; under half that of mice. In the MSA-treated voles, although the plasma insulin concentrations also increased, acetyl-CoA carboxylase activities were not elevated and signs of obesity were not observed.

Acetyl-CoA Carboxylase↗
PubMed1992

Effects of atrial natriuretic peptide on glycerol induced acute renal failure in the rat.

Acute and chronic experiments were performed in rats to examine whether atrial natriuretic peptide (ANP) has any beneficial effects on glycerol-induced acute renal failure (ARF). ANP infusion (Atriopeptin III, 1.0 microgram/kg+0.2 microgram/kg/min) improved the renal blood flow (RBF) and the glomerular filtration rate (GFR), and induced profound natriuresis in the early stage of ARF. By contrast, ANP decreased RBF in the control rats. In addition to these acute hemodynamic effects, long-term beneficial effects of ANP were also observed. A 75-min infusion of ANP significantly lessened the degree of azotemia as well as the extent of renal histologic damage assessed 24 hours after the glycerol injection. These results indicate that ANP can afford partial protection against both acute renal dysfunction and the chronic course of the glycerol-induced ARF, suggesting that ANP may be useful in the treatment of ARF.

Acute Kidney Injury↗
PubMed1991

Three-dimensional structure of ribonuclease Ms*3'-guanylic acid complex at 2.5 A resolution.

The crystal structure of ribonuclease Ms*3'-guanylic acid complex has been determined by molecular replacement methods based on the known structure of ribonuclease T1. The pattern of hydrogen-bonds between the enzyme and the guanine base is similar to that discovered by Arni et al. [( 1988) J. Biol. Chem. 263, 15358-15368] in the crystal structure of ribonuclease T1*2'-guanylic acid complex. As for the possible general base in the trans-phosphorylation step of the catalysis, 0 epsilon 1 of Glu57 is within the hydrogen-bond distance (2.7 A) of the 2'-0 of the nucleotide while N epsilon 2 of His39 is significantly more distant (3.4 A) from the 2'-0.

Amino Acid Sequence↗
PubMed1991

[Cavernous malformation of the brain stem: clinical symptom and its surgical indication].

Clinical features and surgical indication of cavernous malformation (CVM) of the brain stem are reviewed, based on the analysis of five personally encountered cases and nineteen previously reported cases. Nineteen out of these twenty four cases presented sudden onset of neurological deficits suggesting brain stem hemorrhage. Although the majority of those patients with acute onset improved gradually within a couple of weeks, all cases, except for six cases treated with radical removal following their first bleeding episodes, presented recurrent hemorrhages, and one third of them died due to the repeated hemorrhages. The other six cases presented progressive neurological deficits with insidious onset. They were first diagnosed as brain stem gliomas or multiple sclerosis. All except two cases treated with radical removal of the CVM died within a year. Surgical indication of the cerebral CVM is still controversial, because its clinical presentations and natural history have been unclear. Recent clinical application of magnetic resonance imaging enables us not only to make a preoperative diagnosis accurately, but also to evaluate the operability in relation to its anatomical location. Because of an apparent disposition towards repeated hemorrhages, surgical removal should be considered for the symptomatic CVM in the brain stem, on which microsurgical manipulation would be possible with an acceptable risk in many cases.

Adult↗
PubMed1990

Transplantation of the rat pineal organ to the brain: pinealocyte differentiation and innervation.

The pineal organ of neonatal rats was transplanted to the frontal part of the cerebral cortex or the cerebral interhemispheric fissure of an isogenic adult rat to determine whether pineal differentiation and pinealopetal innervation are affected by aberrant neuronal influences. Transplants were fixed for immunohistochemistry at 1, 2 and 6 months after transplantation. When treated with an anti-serotonin antibody, cells in transplants from both locations showed intense immunoreactivity and a morphology comparable to intact pinealocytes, indicating that the transplanted pinealocytes had differentiated normally. Tyrosine hydroxylase immunohistochemistry revealed that new catecholamine fibers of central nervous origin extended only into the periphery and not into the core of transplants grafted within the cortex. However, numerous catecholamine fibers were found in transplants placed in the interhemispheric fissure. These fibers were often accompanied by blood vessels, suggesting that they derived from sympathetic ganglia. Serotonin fibers, which are densely distributed in the cerebral cortex, were seldom found to enter transplants from both locations. These observations indicate that pineal cells express their characteristic properties even when transferred to a foreign milieu and that they do not receive novel innervation from the central nerves that normally do not innervate the intact pineal body; the transplant thereby retains the property of selective pinealopetal innervation.

Animals↗
PubMed1990

Effects of histamine, granulocyte colony-stimulating factor and db-cAMP on the differentiation of HL-60 cells.

Histamine (10(-7) to 10(-3) M) dose-dependently decreased the incorporation of 3H-thymidine into HL-60 cells, starting from the third day of culture. Also, histamine 1 microM significantly induced the differentiation of HL-60 into cells having the morphological characteristics of mature neutrophils, as did db-cAMP and granulocyte colony-stimulating factor (G-CSF). Phosphorylation of proteins appeared at 60 kd and 120 kd was diminished. The phosphorylation profiles induced by G-CSF and db-cAMP were similar to that of histamine. In the case of db-cAMP, however, no phosphorylated band appeared at 120 kd.

Bucladesine↗
PubMed1989

Crystallization of a complex between ribonuclease Ms and 3'-guanylic acid.

The crystals of a complex between ribonuclease Ms, the extracellular ribonuclease from Aspergillus saitoi, and 3'-guanylic acid were obtained from 2-methyl-2,4-pentanediol solution by vapor diffusion technique in the hanging drop mode. The crystals belong to orthorhombic space group P2(1)2(1)2(1) with dimensions a = 47.0 A, b = 62.8 A, c = 37.9 A. The crystals diffract strongly up to at least 2.0 A resolution.

Aspergillus↗