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Biomedical subjects

K Tsukada

Publications and source records attributed to K Tsukada.

At least 163 records · Page 9Linked to original sources
PubMed1994

Liver regeneration is enhanced by omeprazole in rats following partial hepatectomy.

The effect of omeprazole on liver regeneration was studied in rats following partial (65 per cent) hepatectomy. Omeprazole 0.2 mg/kg increased the relative liver weight (weight of liver as a proportion of body-weight) and mitotic index (P < 0.05). There was no difference in food and water intake. The serum gastrin concentration was significantly higher in animals receiving omeprazole 0.2 mg/kg than in controls (P < 0.05). Omeprazole administration induced an increase in the level of serum alkaline phosphatase (P < 0.05) but had no effect on serum albumin, glutamic-pyruvic transaminase and total bilirubin levels. Omeprazole stimulates liver regeneration after partial hepatectomy and this regeneration may be mediated by gastrin.

Animals↗
PubMed1994

OK432 inhibits experimental hepatic metastasis of colon adenocarcinoma ACL-15 in F344 rats.

The effect of OK432 on hepatic metastasis, induced by inoculating 1 x 10(6) ACL-15 cells from a rat colon adenocarcinoma cell line into the ileocolic vein of male F344 rats, was investigated in this study. Metastases were detected 14 days after inoculation in the control rats, however, pretreatment 3 days prior to the tumor cell inoculation with an anti-asialoGM1 antibody, which eliminates natural killer (NK) cell activity in vitro, increased the number of hepatic metastases, shortened the survival time, and decreased the NK activity of the nonparenchymal liver cells (NPC). In contrast, pretreatment with OK432 2 days prior to tumor inoculation significantly decreased the number of hepatic metastases, prolonged the survival time, and augmented the NK activity of the NPC, although treatment with OK432 3 or 7 days after inoculation did not decrease the number of hepatic metastases. Moreover, NPC from the OK432-pretreated rats had a marked antitumor effect against ACL-15 cells in the Winn's neutralization test. The results of this study indicate that pretreatment with OK432 before tumor cell inoculation inhibits hepatic metastasis in this experimental model, possibly by augmentating liver-associated NK activity.

Adenocarcinoma↗
PubMed1994

Enhanced hepatic portal blood flow induced by prostaglandin E1 following liver transplantation in pigs.

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF), and systemic arterial pressure (SAP) were examined after prostaglandin E1 (PGE1) was injected into the vena cava superior (VCS) of liver-transplanted pigs. The injection of PGE1 at 0.2 micrograms/kg/min for 2 min on the day of transplantation and 3 days later produced an increase in PVF without causing any change in HAF or SAP, the response in PVF being dose-dependent. However, no reliable change in PVF, HAF, or SAP was seen when the same dose of PGE1 was administered 7 days after transplantation. Furthermore, no significant difference was noted among the values for PVF and total hepatic blood flow (THF) during the experimented days, although the HAF value had increased markedly 3 days after transplantation. These findings suggest that PGE1 is effective in increasing PVF in the liver transplanted condition; however, the hepatic circulatory improvement attributed to this agent would be limited to the first few days following transplantation.

Alprostadil↗
PubMed1994

Long-term results after nonshunt operations for esophageal varices in children.

The clinical results of nonshunt operations for esophageal varices in 15 children were evaluated. The varices were caused by congenital extrahepatic portal obstruction (EHPO) in 10, liver cirrhosis or fibrosis (C/F) in 3, and idiopathic portal hypertension (IPH) in 2. The operative procedures were transthoracic esophageal transection with paraesophageal devascularization (TR) for 2 EHPO patients under 5 years of age, TR combined with splenectomy and paragastric devascularization (Sugiura procedure) for 11 (8 EHPO, 3 C/F), and splenectomy with devascularization (SP) or splenectomy for the 2 IPH patients. In the EHPO patient under 5 years of age, TR is associated with a likelihood of gastric or esophageal hemorrhage resulting from hypersplenism, gastric congestion, or persistent distal esophageal varices, which can be treated with partial splenic arterial embolization (PSE), endosclerotherapy, or an additional abdominal procedure. The Sugiura procedure has provided satisfactory long-term results, without rebleeding from esophageal varices, in patients with EHPO and C/F for 1 to 20 years. But EHPO patients who undergo the Sugiura procedure before age 6 can have gastric hemorrhage, because of mucosal congestion, for more than 10 years after the procedure, and selective gastric arterial embolization (GAE) might be necessary. In some EHPO patients, especially young ones who have variceal bleeding, a significant increase in hepatopetal portal flow may not develop, but hepatofugal natural shunts may progress. Therefore we recommend direct operative procedures, ie, TR for patients < or = 6 years of age and a one- or two-stage Sugiura procedure for those over 7 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Peritoneal interleukin-6, interleukin-8 and granulocyte elastase activity after elective abdominal surgery.

In this study we investigated the interleukin-8 concentration (IL-8) and granulocyte elastase activity (GE) after elective abdominal surgery. Postoperative interleukin-6 (IL-6), IL-8 concentrations and GE in the peritoneal fluid were examined in 27 patients who underwent various types of elective abdominal surgery. We compared these results with clinical parameters of surgical stress, operating time (OT) and blood loss during the operation (BL). P-IL-6 and P-IL-8 were significantly correlated with OT (P-IL-6; r = 0.67, P < 0.001: P-IL-8; r = 0.59, P < 0.001) and BL (P-IL-6; r = 0.61, P < 0.001: P-IL-8: r = 0.48, P < 0.01). P-IL-8 was significantly correlated with P-IL-6 (r = 0.68, P < 0.001) and there was a positive correlation between GE and P-IL-8 (r = 0.37, P < 0.05). These findings indicate that IL-8 might activate granulocytes in the peritoneal cavity after elective abdominal surgery and that assaying P-IL-6 and P-IL-8 is useful in assessing the host's response to surgical stress.

Abdomen↗
PubMed1994

Endothelin-1 stimulates bile acid secretion and vesicular transport in the isolated perfused rat liver.

The effects of endothelin (ET) on portal pressure and bile secretion were examined using isolated perfused rat liver and rat hepatocyte preparations. ET-1 raised portal pressure dose dependently; administration at a high dose (10(-9) mol) induced a > 200% increase along with reduced bile flow and decreased secretion of bile acid and phospholipids. However, a low dose (10(-10) mol) of ET-1 brought about a < 100% portal pressure rise, enhanced both bile flow and excretion of bile acid and phospholipids, and significantly increased transfer of preadministered horseradish peroxidase (HRP) into bile. In addition, values for Ca2+ concentrations, examined by indo 1 fluorescence, were elevated in isolated hepatocytes after administration of ET-1. Papaverine suppressed the low-dose ET-1 stimulation effects on both portal pressure and bile secretion. Moreover, it also reduced the HRP excretion and suppressed intracellular Ca2+ release. This study demonstrated that ET-1 stimulates vesicular transport, probably via promotion of intracellular Ca2+ release, and, as a result, increases bile acid-dependent bile flow.

Animals↗
PubMed1994

[Thyroid function abnormalities during interferon therapy].

One hundred and twenty patients with chronic hepatitis C were treated with a 6-month course of recombinant alpha-interferon (a daily dose of 6 MU i.m. for the first two weeks and 6 MU or 3 MU i.m. three times weekly thereafter). Serum levels of thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), antithyroglobulin antibody (TGHA) and antimicrosomal antibody (MGHA) were measured before and three month after treatment. Ten of 106 patients with normal thyroid function test before therapy developed thyroid dysfunction; five with hyperthyroidism, four with hypothyroidism and one with positive MCHA. Fourteen patients had thyroid function disorder before treatment. Seven of eight patients with positive MCHA, showed a rise in the titer during the treatment. These data showed that a small proportion of patients treated with interferon developed thyroid dysfunction during the treatment. The interferon-induced thyroid dysfunction appears to be caused via the immune system but also by acting directly on the thyroid gland.

Adult↗
PubMed1994

The association between extrahepatic biliary carcinoma and the junction of the cystic duct and the biliary tree.

OBJECTIVE: To establish accurately the sites of primary extrahepatic biliary carcinomas, so that optimal treatment may be given. DESIGN: Retrospective study. SETTING: University department of surgery. SUBJECTS: 120 patients with 121 primary extrahepatic biliary carcinomas. MAIN OUTCOME MEASURES: Site of tumour (primary site being geometric centre of tumour) and distance from junction of cystic duct and the biliary tree on histological examination of the resected specimen. RESULTS: 64 of the tumours (53%) were within 5 mm of the junction; 14 were proximal to the junction, 32 distal, and 18 within the cystic duct itself. CONCLUSIONS: Over half the primary extrahepatic biliary tumours were within 5 mm of the junction of the cystic duct and the rest of the biliary tree. Further investigations are required to find out if any particular aetiological factor can be identified.

Adenocarcinoma↗
PubMed1994

Inhibition of ethanol-induced inositol phosphate formation and Ca(2+) mobilization by okadaic acid in rat hepatocytes: evidence for a role of protein phosphatases in the modulation of phospholipase C by ethanol.

The effect of the protein phosphatase inhibitor okadaic acid on phospholipase C (PLC)-linked signal transduction processes was investigated in intact hepatocytes. A short (5 min) pretreatment of the hepatocytes with okadaic acid (1 mu M) markedly inhibited a subsequent stimulation of PLC by ethanol as well as by receptor-mediated stimuli (vasopressin and phenylephrine). Okadaic acid inhibited the agonist-induced hydrolysis of polyphosphoinositides, the accumulation of inositol trisphosphate (InsP(3)) and the increase in cytosolic Ca(2+) concentrations. The inhibition could be overcome by high concentrations of vasopressin or ethanol, but only partly so with phenylephrine. A comparison of the sensitivity of different agonists at similar rates of InsP(3) accumulation and Ca(2+) mobilization indicated that ethanol-induced PLC activation was more resistant to the effects of okadaic acid than the hormonal agonists. Moreover, the stimulation of PtdInsP kinase by ethanol, which accompanies PLC activation, was refractory to okadaic acid treatment. These findings suggest that receptor-mediated PLC activation is subject to multiple controls by phosphorylation-dephosphorylation, not all of which affect the actions of ethanol on this signal transduction system.

Animals↗
PubMed1993

Expression of active human DNA ligase I in Escherichia coli cells that harbor a full-length DNA ligase I cDNA construct.

A recombinant plasmid for expression of full-length human DNA ligase I (phLig-I) was constructed in a plasmid/phage chimeric vector, pTD-T7N, which was derived from pUC118 by oligonucleotide-directed mutagenesis. The insert contained a 2757-base pair coding sequence for a whole human DNA ligase I and an extra ACC codon adjacent to the ATG initiation codon. This ACC codon was required for achieving high levels of expression of full-length DNA ligase I in Escherichia coli strain BL21. The recombinant plasmid, which was designed to exploit the T7 late promoter and the ATG initiation codon for beta-galactosidase was transfected into E. coli BL21 cells that express T7 RNA polymerase. The recombinant clone produced relatively high levels of DNA ligase I with a molecular mass of 130 kDa, as estimated by SDS-polyacrylamide gel electrophoresis. The DNA ligase was purified to near-homogeneity by the two-step column chromatographic procedure from BLphLig-I cells that had been induced with isopropyl beta-D-thiogalactoside. The specific activity, chromatographic behavior, kinetic properties, molecular mass, and antigenicity of the recombinant human DNA ligase I were indistinguishable from those of purified mammalian DNA ligase I. Metabolically labeling experiments with 32P(i) indicate that the recombinant DNA ligase I was present as an enzyme-AMP reaction intermediate, but not as a phosphoprotein, in the E. coli cells.

Amino Acid Sequence↗
PubMed1993

Expression of non-hepatic-type S-adenosylmethionine synthetase isozyme in rat hepatomas induced by 3'-methyl-4-dimethylaminoazobenzene.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, non-hepatic-type and liver-type enzymes, which are the products of two different genes. We have examined the expression of two AdoMet synthetase isozyme proteins and mRNAs in rat hepatomas induced by 3'-Me-DAB. The levels of non-hepatic-type enzyme protein and mRNA are clearly induced by 3'-Me-DAB feeding. On the other hand, the levels of liver-type enzyme protein and mRNA are nearly the same or slightly decreased during hepatocarcinogenesis. These results indicate that the expression of the non-hepatic-type isozyme gene is obviously influenced with the progression of carcinogenesis and that the non-hepatic-type isozyme is useful as a oncodevelopmental marker in the liver.

Amino Acid Sequence↗
PubMed1993

A new brain-specific 14-kDa protein is a phosphoprotein. Its complete amino acid sequence and evidence for phosphorylation.

We previously reported a new brain-specific protein with a molecular mass of 14 kDa, specifically present in synapses around neurons but not in glial cells [Nakajo, S., Omata, K., Aiuchi, T., Shibayama, T., Okahashi, I., Ochiai, H., Nakai, Y., Nakaya, K. & Nakamura, Y. (1990) J. Neurochem. 55, 2031-2038]. In the present study, we determined the primary structure of this protein, found that it is phosphorylated in vitro and in vivo, and designated it phosphoneuroprotein 14 (PNP 14). The protein is a single polypeptide with 134 amino acid residues (molecular mass = 14122 Da), and it contains a hydrophobic region at the center of the molecule. The carboxy-terminal region has all seven proline residues, and is rich in glutamic acid, which contribute to the acidic property of the protein. The amino-terminal region possesses four unique repetitive motifs, Glu(Ser)-Lys-Thr-Lys-Glu(Gln)-Gly(Gln)-Val(Ala). When a cytosolic fraction prepared from rat cerebral cortex was incubated with [gamma-32P]ATP, 32P was incorporated into PNP 14. Phosphorylated PNP 14 was immunoprecipitated from rat brain synaptosomes labeled metabolically with [32P]orthophosphate. Injection of [32P]orthophosphate into the third ventricle of rat brain resulted in incorporation of radioactive phosphate into PNP 14. We have also found that Ca2+, calmodulin-dependent protein kinase II phosphorylates serine residue(s) of PNP 14 in vitro. The results suggest that PNP 14 may be important to neuronal cells, but not to glial cells, and that its physiological functions may be controlled by the phosphorylation reaction.

Amino Acid Sequence↗
PubMed1993

Immunohistochemical analysis of rat S-adenosylmethionine synthetase isozymes in developmental liver.

Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, liver-type and kidney(non-hepatic)-type enzymes. The developmental expression of these two isozymes proteins has been investigated in rat liver using immunohistochemical techniques. The liver-type AdoMet synthetase is expressed only in adult liver, but not in fetal liver. On the other hand, the kidney-type AdoMet synthetase is predominantly expressed in fetal liver and faintly detected in adult liver. It was also found that both isozymes were localized to the hepatocytes of rat liver. These results clearly show that AdoMet synthetase isozymes are developmentally regulated within hepatocytes. In addition, in rat kidney we have shown that the kidney-type AdoMet synthetase is predominantly localized to the distal tubule.

Amino Acid Sequence↗
PubMed1993

Percutaneous transhepatic cholecystostomy for acute acalculous cholecystitis.

The effectiveness and long-term results of percutaneous cholecystostomy for acute acalculous cholecystitis are evaluated. Fifteen patients with acute acalculous cholecystitis were treated prospectively by this procedure, using a pigtail catheter successfully placed under ultrasonographic and fluoroscopic guidance. Prompt relief of the signs and symptoms of cholecystitis was achieved in 14 patients. One required emergency cholecystectomy for uncontrolled bleeding after drainage. Another patient underwent prophylactic cholecystectomy before further chemotherapy for leukaemia. The remaining 13 patients required no further surgery. Morbidity and mortality rates were 13 per cent and nil respectively. Long-term follow-up showed no recurrence of cholecystitis after removal of the catheter. Percutaneous cholecystostomy is a safe, effective and usually definitive procedure for the treatment of acute acalculous cholecystitis.

Acute Disease↗
PubMed1993

High carrier rate after hepatitis B virus infection in the elderly.

An outbreak of hepatitis B virus infection occurred in a nursing facility; it involved 31 patients with sequelae of cerebral vascular accidents (15 men and 16 women; mean age, 77.4 +/- 9.3 yr). HBsAg disappeared within 6 mo in 9 patients and persisted during an observation period of more than 6 mo in 13; the remaining 9 patients were lost to follow-up while they carried HBsAg. Thus 13 of 22 patients followed (59%) became HBsAg carriers. We amplified a part of the S gene (436 nucleotides) with polymerase chain reaction on hepatitis B virus DNA from 12 randomly selected patients. The sequences of nine patients were the same as that of a nursing assistant who was an HBsAg carrier and suspected as the source of infection; it differed by only 1 or 2 (< 0.5%) nucleotides from those of the remaining three patients. Between the group of nine patients with transient HBV infection and the 13 patients with persistent HBV infection, we found no differences in age or sex or in parameters of nutrition or immunocompetence. These results indicate a high incidence of HBV carrier state in the elderly.

Adolescent↗
PubMed1993

A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats.

Portal venous flow (PVF) and portal venous pressure (PVP) were examined after the jugular or portal injection of Prostaglandin E1 (PGE) in rats partially hepatectomized by either 40% or 66%. In the 66% hepatectomized animals, the jugular injection of PGE at 5.0 micrograms/kg/min produced an increase in PVF concomitant with a fall in systemic arterial pressure (SAP), while PVP remained unchanged. The portal injection of PGE at 0.5 micrograms/kg/min increased PVF to a level equivalent to that evoked by the jugular injection of 5.0 micrograms/kg/min PGE, without any change in SAP. PVP was reduced synchronistically with an increase in PVF. The PVF response to a portal injection of PGE at 0.5 micrograms/kg/min was not reproduced in liver intact rats. These results suggest that PGE is potent in increasing PVF in the partially resected condition of the liver and that the portal vascular bed is involved in this response.

Alprostadil↗
PubMed1993

Enhanced liver regeneration in rats treated with 15-deoxyspergualin alone and in combination with FK 506.

The effects of 15-deoxyspergualin (DSG) alone and in combination with FK 506 (FK) on liver regeneration after 2/3 hepatectomy was studied. The administration of 5 mg/kg DSG increased the liver weight as a percentage of the body weight (RLW) in the 5 days following the hepatectomy. This enhanced regeneration was not affected if interleukin(IL)-2 was also given. The combination of 1 mg/kg DSG and 0.05 mg/kg FK induced the highest values for RLW. The amounts of food and water intake increased in the DSG and FK combined group. Blood chemistry indicated that the combined administration of DSG and FK could reduce side-effects more effectively than separate administration. These observation led us to conclude that DSG has a stimulating potency in liver regeneration by means of direct suppression of T cell activation, and there is a synergistic effect on regeneration by DSG and FK.

Animals↗