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Biomedical subjects

S Otani

Publications and source records attributed to S Otani.

At least 19 recordsLinked to original sources

Posttranslational regulation of spermidine/spermine N1-acetyltransferase with stress.

The effect of stress on the activity and level of mRNA of spermidine/spermine N1-acetyltransferase (SAT), a polyamine degradation rate-limiting enzyme, was studied in Ehrlich ascites tumor cells. When the cells were treated with sodium arsenite or ethanol for 1 h at 37 degrees C, the activity of SAT increased time- and dose-dependently. Total RNA was isolated from cells treated with stress, and the relative abundance of the SAT mRNA was measured by Northern blot analysis. The amount was comparable to those in control cells. In stress-treated cells, the biological half-life of the enzyme was 48-55 min, but 27-30 min in control cells. When cells were treated with arsenite in the presence of cycloheximide, enzyme activity did not increase. In those cells, half-life of the enzyme was shorter than in the cells treated with arsenite alone. This suggests that stress-treatment of cells enhanced SAT activity posttranslationally and that some factor(s) which was synthesized de novo during the treatment of arsenite is involved in the stabilization of the enzyme.

Acetyltransferases

Detection of hepatitis C virus antibody in the absence of viral RNA in patients with autoimmune hepatitis.

OBJECTIVE: To determine whether laboratory findings showing antibodies to hepatitis C virus (HCV) in patients with autoimmune hepatitis represent false-positive results and to identify possible explanations for true-positive results in these patients. DESIGN: Cross-sectional. SETTING: University-based hospital. PATIENTS: Fifty-two patients with non-A, non-B chronic hepatitis as a control group and 26 patients with classic chronic active autoimmune hepatitis. MEASUREMENTS: Comparison of the results of five kinds of assays of HCV antibodies and HCV RNA. MAIN RESULTS: Of 52 patients with non-A, non-B chronic hepatitis, HCV antibodies (anti-HCV) were detected in 42 patients (81%; 95% CI, 67% to 90%) by a first-generation enzyme-linked immunosorbent assay (ELISA-I), in 39 patients (75%) by Sp42 ELISA, in 37 patients (71%) by RIA-I, in 49 patients (94%) by ELISA-II, and in 48 patients (92%) by RIBA-II. We found HCV RNA in 47 patients (90%; CI, 79% to 97%). Of the 26 patients with autoimmune hepatitis, anti-HCV were detected in 23 patients (88%; CI, 70% to 98%) by ELISA-I, in 12 (46%) by both RIA-I and Sp42 ELISA, in 20 (77%) by ELISA-II, and in 9 (35%) by RIBA-II. However, HCV RNA was found in only five of these patients (19%; CI, 7% to 39%). None of our patients, including controls, had antibodies to superoxide dismutase. Of the 21 patients who had autoimmune hepatitis that was completely responsive to steroid therapy, 18 had anti-HCV by ELISA-I, but 13 of these patients had negative results by RIBA-II, and only two patients had HCV RNA. Of the five patients who did not respond to steroid treatment, all had anti-HCV by ELISA-I, four had negative results by RIBA-II, and three had HCV RNA. CONCLUSIONS: Testing for HCV antibodies in patients with autoimmune hepatitis frequently elicits positive results when the ELISA-I or ELISA-II tests are used. Most of these appear to represent false-positive results because HCV RNA is usually absent from the serum. Such false positivity may result from previous infection with HCV or from cross-reaction of an epitope of HCV. Other patients with apparent autoimmune hepatitis who fail to respond to corticosteroid therapy may actually have chronic hepatitis C (or other non-A, non-B hepatitis) infection.

Adult

Enhancement of spermidine/spermine N1-acetyltransferase activity by treatment with lithium chloride in Ehrlich ascites tumor cells.

The activity of spermidine/spermine N1-acetyltransferase (SAT) was enhanced in Ehrlich ascites tumor cells by the addition of lithium chloride. Na+ did not affect the enzyme activity. Total RNA was isolated from cells treated with LiCl and the relative abundance of the SAT mRNA was measured by Northern blot analysis. The levels in cells treated with LiCl were comparable to those in control cells. In the treated cells, the biological half-life of SAT was approximately 20 min, which was the same as for control cells. When LiCl and H-7, a protein kinase inhibitor, were added simultaneously to culture, the elevation caused by LiCl of SAT activity was reduced. LiCl did not cause maximum enhancement of the enzyme in cells treated beforehand with a higher concentration of TPA. These results suggest that treatment of Ehrlich ascites tumor cells with LiCl enhanced SAT activity during translation, not during transcription or after translation and that the enhancement of SAT by LiCl is probably mediated by protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Enhancement of extracellular protein concentrations during long-term potentiation in the rat hippocampal slice.

The possibility that the enhancement of extracellular protein concentrations during long-term potentiation is related to the maintenance of long-term potentiation was examined in area CA1 of rat hippocampal slices. First, we found that during the 3 h after induction, long-term potentiation maintenance was correlated with a persistent enhancement of extracellular protein concentrations. Second, when the protein synthesis inhibitor cycloheximide was applied 10-15 min before long-term potentiation induction, the drug blocked both the maintenance of long-term potentiation and the elevation of extracellular protein concentrations. These results suggest that the elevation of extracellular protein concentrations requires new protein synthesis. The results further indicate that the newly synthesized proteins may play a role in the maintenance of long-term potentiation.

2-Amino-5-phosphonovalerate

Effect of Gomisin A (TJN-101) on liver regeneration.

We studied the effect of TJN-101, a lignan component of Schisandra fruits (Schisandrae fructus), on liver regeneration after partial hepatectomy. TJN-101 was given orally to male Wistar rats 30 min before partial hepatectomy. The mitotic index and the level of DNA synthesis increased after partial hepatectomy and their increase was significantly enhanced by TJN-101. Ornithine decarboxylase (ODC) activity increased in the early stages of liver regeneration and it was also significantly enhanced by TJN-101. Besides, TJN-101 enhanced the increase in hepatic putrescine. These results suggest that TJN-101 stimulates liver regeneration after partial hepatectomy by enhancing ODC activity, which is an important biochemical event in the early stages of liver regeneration.

Animals

Effects of butylated hydroxyanisole on ornithine decarboxylase activity induced by ultraviolet-B and PUVA in mouse skin.

The effects of butylated hydroxyanisole (BHA), a representative phenolic antioxidant, on the activity of ornithine decarboxylase (ODC, an indicator of tumor promotion and epidermal hyperproliferation) induced by ultraviolet-B (UVB) or PUVA in mouse skin were investigated. By topical application of BHA (55 mumol), PUVA-induced ODC activity was suppressed by about 60% at both 12 h and 24 h after treatment. In contrast, BHA failed to suppress UVB-induced ODC activity in mouse skin. These results suggest that the induction of ODC activity by UVB or PUVA is mediated by different pathways.

Animals

Spermidine/spermine N1-acetyltransferase, a new biochemical marker for epithelial proliferation in rat bladder.

We examined the activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme of the biodegradation of polyamines, in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced transitional cell carcinoma (TCC) and melamine-induced papillomatosis of rat bladder, and compared the activity to that of ornithine decarboxylase (ODC). Both activities were higher in both lesions than in control rats. The difference between SAT and ODC activities in cancerous tissue and papillomatosis was not significant. Cells stained for proliferating cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with much PCNA. The results indicated that an elevation of SAT activity occurs in both reversible and irreversible proliferation of bladder epithelium and could be important in bladder carcinogenesis.

Acetyltransferases

[A successful two-staged Fontan procedure for tricuspid atresia with bilateral superior venae cavae and left pulmonary arterial stenosis].

A 10-year-old boy with tricuspid atresia (type I-b), bilateral superior venae cavae and left pulmonary arterial branch stenosis was treated successfully by a two-staged Fontan procedure. At 7 years of age, left Glenn shunt was performed after creation of a communicating vessel between the right and left superior vena cava, using a GORE-TEX graft of 10 mm of diameter. Three years later, after having confirmed graft patency, Fontan procedure was achieved without any problems. We think the innominate vein creation by an artificial material was a key design for the following successful two-staged Fontan procedure in this case.

Blood Vessel Prosthesis

[Late results of the subclavian flap repair for aortic coarctation-effects on the left upper limb].

Late results of the subclavian flap repair for the aortic coarctation and effects on the left upper limb were evaluated on 9 patients who were operated on and had been continuously followed up at Hyogo Kenritsu Amagasaki Hospital. Their mean age at operation was 2.3 years (range 9 days-5.7 years), and mean follow-up period 5.9 years (range 3.1 years-8.3 years). Reoperation for restenosis was necessary in one patient and it proved the initial aortotomy and patch angioplasty had not been extended sufficiently beyond the stenotic segment. In the remaining 8 patients, the mean values of arm-to-leg systolic pressure gradient and peak flow velocity at the descending aorta by Doppler echocardiogram were 2.5 mmHg and 1.9 m/sec respectively. Length and arm circumference of the left upper limb were all significantly shorter than those of the right side. The left systolic brachial pressure and core temperature of the hand were also significantly low comparing with those of the right side. No patients, however, complained the ischemic symptoms of the left upper limb. In conclusion, the subclavian flap repair is thought to be a safe and long effective procedure for the aortic coarctation.

Adolescent

Polyamine metabolism in colonic mucosa from patients with ulcerative colitis.

Polyamine metabolism in mucosa both from patients in the active or remission stage of ulcerative colitis (UC) and from healthy controls was studied. In the active stage of UC, mucosal spermidine concentration was higher than in remission or in the controls, but the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, rate-limiting enzymes of polyamine biosynthesis, were lower. In the active stage of UC, the mucosal level of mRNA coding for ornithine decarboxylase was lower than in the remission stage of UC or in the controls. The activity of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme of polyamine degradation, was higher in the active stage of UC than in the remission stage of UC or in the controls. However, it seemed that this activity did not reflect the increase in the spermidine concentration. The results showed that the spermidine increase in the active stage of UC was not due to changes in the synthesis or degradation of polyamines; the increase may have been due to increased exogenous spermidine uptake.

Acetyltransferases

[Cardiac strangulation with permanent epicardial pacemaker lead].

A 3-year-old boy underwent corrective surgery for tetralogy of Fallot. During the operation, permanent epicardial pacemaker leads were implanted for complete A-V block, which was transient and a generator implantation was not necessary. The postoperative course was uneventful and he had been doing well until nine years of age, when he was admitted to our hospital with general fatigue. The data of echo cardiogram and cardiac catheterization showed the biventricular heart failure with right ventricular outflow tract obstruction (RVOTO). Because of his rapid deterioration refractory to the intensive medical therapy, semi-emergency surgery was recommended to relieve his RVOTO. It was found during the operation that the looped pacemaker leads had carved deeply in the atrioventricular groove, so that compressed the main pulmonary artery, left main coronary artery and encircled left ventricle. The pacemaker leads were dissected as long as possible, and cut segmentally. Additionally a patch enlargement of the main pulmonary artery was necessary to relieve the residual stenosis. Although IABP support was needed in a while, his postoperative course was uneventful, and postoperative examinations showed normal cardiac function. This rare complication, so called "cardiac strangulation", should be in mind when the implantation of permanent pacemaker leads is indicated in pediatric cases.

Child

Polyamine levels in synovial tissues and synovial fluids of patients with rheumatoid arthritis.

We determined the polyamine contents of the synovial tissues from 11 patients with rheumatoid arthritis (RA), and the free putrescine levels in the synovial fluids (SF) from 10 patients with RA, 7 with osteoarthritis (OA), 5 with posttraumatic arthritis, and 3 with infectious arthritis. Putrescine levels in the synovial tissues correlated with serum C reactive protein concentration in patients with RA. Free putrescine levels in SF were significantly elevated in patients with infectious arthritis, compared with those found in RA, OA, and posttraumatic arthritis. Free putrescine levels in SF from patients with RA were significantly higher than in those with OA. Our findings suggest that polyamines may play an important role in RA.

Adult

[Studies on changes in low esophageal sphincter function after esophageal transection or esophago-esophagostomy in children].

An aim of the present study is to clarify the changes of esophageal function after surgical treatments of the esophageal varices or the congenital esophageal stenosis in children. Esophageal manometric studies were performed in sixteen children undergoing the esophageal transection with paraesophageal devascularization or the esophago-esophagostomy with partial esophagectomy before, within 1 month and over 7 months after the operation. The pressure of lower esophageal sphincter (LES), the length of LES, the LES relaxation test and the gastroesophageal reflux (GER) inducing test were measured. 1) Esophageal transection; The pressure dropped within 1 month and returned to the preoperative level over 11 months after the operation. Temporal deterioration of LES function was observed during the early postoperative days. However, return to the preoperative state was gained over 1 year. 2) Esophago-esophagostomy; The pressure and the length of LES were not changed after the operation. The LES function was disturbed preoperatively and moreover long postoperatively, in the case when congenital stenosis closely existed to the esophago-gastric junction. Degree of the postoperative disturbance of the LES function may be influenced by the distance to the part of the transection or the partial esophagectomy from the E-C junction.

Anastomosis, Surgical

Rapid activation of hippocampal casein kinase II during long-term potentiation.

Several studies suggest that protein kinase C and type II Ca2+/calmodulin-dependent protein kinase are activated during induction of long-term potentiation (LTP). We now report that casein kinase II (CK-II), which is present in high concentration in the hippocampus, is also activated in the CA1 region during LTP. CK-II activity increased within 2 min after a train of high-frequency electrical stimulations and reached a maximum (2-fold increase) 5 min later before returning to baseline value. The stimulated protein kinase activity, which was blocked by a selective antagonist of N-methyl-D-aspartate receptors, exhibited specific properties of CK-II, including phosphorylation of the specific substrates of CK-II, marked inhibition by a low heparin concentration, and the use of GTP as a phosphate donor. CK-II activity was also selectively and rapidly augmented in another form of LTP produced by bath application of tetraethylammonium; this LTP (called LTPk) is Ca2+ dependent but N-methyl-D-aspartate independent. Phosphorylation of casein that was not inhibited by heparin (i.e., casein kinase I) remained unchanged. We suggest that an increase in CK-II activity is important in LTP induction.

Adenosine Triphosphate

Reduction by interferon-alpha of levels of c-myc protein and DNA synthesis in a human hepatoma cell line mediated by inhibition of putrescine synthesis.

Interferon-alpha inhibited increases in ornithine decarboxylase, intracellular putrescine, and DNA synthesis as human hepatoma cells were stimulated to grow. Interferon-alpha inhibited the increase in the c-myc protein level, but not its mRNA level. Added putrescine abrogated the effects on c-myc protein and DNA synthesis. Interferon-alpha seemed to inhibit the increase in the c-myc protein level post-transcriptionally by reducing the putrescine level, inhibiting DNA synthesis.

Blotting, Northern

Effects of parathyroid hormone on ornithine decarboxylase activity in human osteosarcoma cells.

Ornithine decarboxylase (ODC) is a rate-limiting enzyme of the biosynthesis of polyamines, which are important in cell growth and differentiation. Here, we studied whether parathyroid hormone (PTH) affects the induction of ODC and the proliferation of the human osteoblast-like cell line SaOS2, which is sensitive to PTH. In confluent cells, ODC activity was not detected, but activity was significantly induced by fresh medium, with maximum activity 6 h after the change. PTH potentiated this enzyme induction in a dose-dependent manner at 10(-9) and 10(-8) M at which range the intracellular cAMP level also rose. Dibutyryl cAMP, cholera toxin, and 3-isobutyl-1-methylxanthine each caused an increase in ODC activity similar to that with PTH. The half-life of enzyme activity was about 30 min and was not changed by the addition of PTH. mRNA coding for ODC was detected in the confluent cells and its concentration was increased two- to threefold by the fresh medium. No further increase in mRNA occurred when PTH was added. At 48 h after the change of medium, PTH inhibited the DNA synthesis induced by fresh medium. These results suggest that the increase in ODC activity caused by PTH was caused by enhancement of cAMP synthesis, and that this augmentation involves post-transcriptional regulation.

Bucladesine

Control by treatment with lithium chloride of ornithine decarboxylase in Ehrlich ascites tumor cells.

The activity of ornithine decarboxylase (ODC) was increased in Ehrlich ascites tumor cells by a change of the medium. This increase in the activity was inhibited by the addition of LiCl to the medium. Na+ and Mg2+ did not affect the enzyme activity. The inhibition of the enzyme activity with LiCl was not reversed by the addition of inositol or dibutyryl cyclic AMP. Total RNA was isolated from cells treated with LiCl and the relative abundance of the ODC mRNA was measured by Northern blot analysis. These levels in cells treated with LiCl were comparable to those in control cells. In the treated cells, the biological half-life of ODC was 14 min, which was the same as for the control cells. The inhibition by LiCl of ODC activity was not due to the nonspecific toxicity of LiCl. These results suggest that treatment of Ehrlich ascites tumor cells with LiCl suppressed ODC induction during translation, not during transcription or after translation.

Animals