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Biomedical subjects

T Nakai

Publications and source records attributed to T Nakai.

At least 163 records · Page 9Linked to original sources
PubMed1997

Importance of microperineural invasion as a prognostic factor in ampullary carcinoma.

BACKGROUND: This was a study of the relation of clinicopathological factors to prognosis in 25 patients who had ampullary carcinoma resected. METHODS: The 5-year survival rate was six of the 25 patients. The presence of microperineural invasion was sought and related to outcome. RESULTS: Factors relating to prognosis included tumour gross appearance, diameter, pancreatic invasion and microperineural invasion. The 5-year survival rate of 14 patients with microperineural invasion was 3, significantly worse than the 7 in 11 without invasion (P = 0.002, univariate analysis). By multivariate analysis, microperineural invasion was the most important prognostic factor (P = 0.02). Type of tumour recurrence was similar to that in pancreatic carcinoma. CONCLUSION: Pancreaticoduodenectomy, rather than local resection, is the procedure of choice in patients with ampullary carcinoma.

Aged↗
PubMed1997

Effect of oxidized low density lipoprotein on thrombomodulin expression by THP-1 cells.

We have investigated the effects of oxidized low density lipoproteins (oxidized LDL) on the expression of TM by THP-1 monocytic cells. TM antigen levels and its cofactor activity for thrombin-dependent protein C activation were increased by oxidized LDL and accompanied by an increase in TM mRNA levels. Incubation of THP-1 cells with 300 microg/ml oxidized LDL for 24 h resulted in an 80% increase of cellular TM antigen levels. Native LDL and acetylated LDL did not affect the TM expression by these cells. The resultant aqueous phase after extraction of oxidized LDL by chloroform/methanol increased the TM antigen levels as well as oxidized LDL. Phorbol 12-myristate 13-acetate (PMA) also increased the TM antigen level 2.1 times the control and was accompanied by the adhesion of cells to plastic dishes and increasing macrophage cell surface antigen CD14 levels. In contrast, oxidized LDL did not induce differentiation to the macrophage. The present results indicate that oxidized LDL increases cellular TM antigen without cellular differentiation and that up-regulation of TM by oxidized LDL in monocytes may have some implication in atherosclerosis.

Arteriosclerosis↗
PubMed1997

[Use of BiPAP during weaning from mechanical ventilation in a patient with chronic obstructive pulmonary disease and acute respiratory failure].

In a 65-year-old man with chronic obstructive pulmonary disease and acute respiratory failure, bi-level positive airway pressure device (BiPAP) was used as part of weaning from mechanical ventilation. As an outpatient, he had had dyspnea of grade V (Hugh-Jones) and was hypercapnic (PaCO2 of 70 torr) and hypoxemic (PaO2 of 60 torr), while he was receiving oxygen at 2 L/min via nasal cannula. Acute respiratory failure developed due to pneumonia, and mechanical ventilation was begun. However, he could not be weaned with a standard weaning technique (T-piece). On the fifth day of mechanical ventilation, he was extubated and treatment with BiPAP was begun. He did not complain of dyspnea even though PaCO2 did not decrease, which indicates that BiPAP reduced the work of breathing. Use of BiPAP might make reintubation unnecessary when acute ventilatory failure develops soon after extubation in patients with COPD.

Acute Disease↗
PubMed1996

Effect of glucose, insulin, and insulin-like growth factor-I on glucose transport activity in cultured rat vascular smooth muscle cells.

Glucose transport activity in cultured rat vascular smooth muscle cells (VSMCs) was examined under various concentrations of D-glucose, insulin, and insulin-like growth factor-I (IGF-I). Confluent cultures of VSMCs were incubated with serum-free medium containing 0-25 mmol/l of D-glucose for 24-49 h. The basal rate of 2-deoxyglucose uptake was reduced in association with increasing concentrations of D-glucose. Uptake of 2-deoxyglucose into the cells was linear between 0 and 15 min of incubation regardless of the glucose concentration. The uptake was inhibited by the addition of 10 mumol/l cytochalasin B or 100 mmol/l D-glucose indicating that the effects were mediated by specific integral glucose carriers. The effect of D-glucose was time-dependent and reversible. Insulin increased the uptake of 2-deoxyglucose in a dose-dependent manner, and its effect was dependent on the preincubation dose of D-glucose. Insulin-stimulated uptake was lower in the cells pre-exposed to 25 mmol/l D-glucose than in the cells pre-exposed to concentrations of D-glucose below 5.5 mmol/l. After a long-term incubation with insulin, the insulin-stimulated glucose transport was inhibited. Recovery of glucose transport activity was assessed by incubating cells with D-glucose for 24-48 h to induce desensitization. After a 24 h glucose conditioning, the uptake of 2-deoxyglucose was lower in the cells preincubated with 25 mmol/l glucose than in the cells preincubated with 5.5 mmol/l glucose. The effect of the glucose conditioning was reversible and dependent on the preincubation dose of D-glucose. IGF-I was a more potent stimulator of glucose transport than insulin. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), inhibited the uptake of glucose stimulated by insulin or IGF-I in a dose-dependent manner. Our results suggest that D-glucose regulates its own uptake independently of insulin and modulates the ability of insulin to induce insulin resistance in the cultured rat VSMCs. Glucose attenuated the effect of insulin, and led to a progressive decrease in the activity of the glucose transport effector system. Activation of wortmannin-sensitive PI3-kinase may be involved in the signaling pathways of the insulin- and IGF-I-stimulated glucose uptake in VSMCs. This mechanism of insulin resistance may be relevant to the formation of cellular defects in the vascular wall in patients with diabetes mellitus.

Androstadienes↗
PubMed1996

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3.

The VLDL receptor, a newly identified lipoprotein receptor, recognizes apoE containing lipoproteins. The human VLDL receptor was overexpressed in 1d1A-7, a mutant Chinese hamster ovary cells lacking LDL receptors. Each VLDL obtained from a normolipidemic subject with two epsilon3 or epsilon2 alleles similarly competed for the binding of radiolabeled rabbit beta-VLDL to the VLDL receptors. The anti-apoE monoclonal antibody 1D7, which inhibited binding of apoE3 to the LDL receptors, failed to compete for the binding of VLDL (apoE3 or apoE2) to the VLDL receptors. Results indicate that the binding site of apoE on the VLDL receptor may differ from its binding site on the LDL receptor.

Animals↗
PubMed1996

Improved liver function following infusion of fructose-1, 6-bisphosphate in posthepatectomy patients.

The clinical effect of fructose-1,6-bisphosphate (FBP) administered to posthepatectomy patients was examined. FBP at 0.25 mmol/kg was administered continuously into the hepatic artery for 60 minutes on the 1st postoperative day in 11 cases. Hepatic arterial infusion of 0.25 mmol/kg glucose was performed in 7 cases. Furthermore, in 10 cases in which a catheter was not inserted in to the hepatic artery, 0.25 mmol/kg FBP was administered intravenously over a 60-minute period. Arterial ketone body ratio (AKBR) and serum levels of cyclic adenosine monophosphate, immunoreactive insulin, inorganic phosphorus, glucose, fructose, pyruvate, lactate and pyruvate kinase (PK) in the arterial blood were measured before and after administration. AKBR hardly changed after hepatic arterial infusion of glucose. It rose until 3 hours after intravenous or intrahepatic arterial administration of FBP. Especially, after hepatic arterial infusion of FBP, the AKBR was significantly higher up to 2 hours after administration than that before administration (P < 0.01). With hepatic arterial infusion of FBP, serum pyruvate transiently increased immediately after infusion (P < 0.01). PK activity was significantly elevated after administration of FBP (P < 0.05). Serum lactate levels decreased significantly after hepatic arterial infusion of FBP (P < 0.05). There was no difference in the recovery of protein synthetic ability and the postoperative changes in serum liver function test values among the three groups. Hepatic arterial infusion of FBP was suggested to promote adenosine triphosphate production by acceleration of the glycolytic pathway and lactate uptake in the hepatic cell.

Blood Glucose↗
PubMed1996

Usefulness of ultrasound-guided, fine-needle aspiration biopsy for palpable breast tumors.

OBJECTIVE: To investigate whether ultrasound (US) guidance improves the sensitivity of fine-needle aspiration biopsy (FNAB) in patients with palpable breast tumors. DESIGN: A retrospective study. SETTING: A university hospital. PATIENTS: A total of 107 patients with breast tumors (114 lesions) underwent US-guided FNAB and 138 patients (143 lesions) underwent FNAB guided by palpation (standard FNAB). MAIN OUTCOME MEASURES: The diagnoses obtained by FNAB were compared with the surgical findings and the diagnostic value of US-guided FNAB was evaluated. RESULTS: The sensitivity of US-guided FNAB was 89.3%, the specificity was 82.9%, and the accuracy was 86.9%. In contrast, the sensitivity of standard FNAB was 61.1%, the specificity was 73.3%, and the accuracy was 65.0%. For breast tumors 2.0 cm or less in diameter, the sensitivity and accuracy of US-guided FNAB were significantly higher than those of standard FNAB. CONCLUSION: Ultrasound-guided FNAB can improve the preoperative diagnosis of breast cancer, especially in patients with tumors that are 2 cm or less in diameter.

Biopsy, Needle↗
PubMed1996

Role of nitric oxide and superoxide anion in leukotoxin-, 9,10-epoxy-12-octadecenoate-induced mitochondrial dysfunction.

The present study was carried out to explore the involvement of nitric oxide (NO) and superoxide anion (O2.-) in Leukotoxin (Lx)-induced suppression of mitochondrial respiration. Glutamate- and succinate-dependent oxygen consumption and cytochrome c oxidase activity were assayed. Lx-induced mitochondrial damage was significantly attenuated by the pretreatment of lung with 4 x 10(-4) M NG-monomethyl-L-arginine (L-NMMA) or 500 units/ml superoxide dismutase (SOD) in ex vivo. However, L-NMMA plus SOD pretreatment showed no additive effect on the recovery of mitochondrial functions. The same assay was performed after the exposure of intact mitochondria to NO containing solution (1.25 x 10(-5) M) or 0.1 mM KO2/18-Crown-6 solution, which generated O2.-(6.4 x 10(-5) M). NO, but not O2.-, significantly inhibited the respiration of isolated mitochondria in vitro. Thus, there were great discrepancies in the involvement of NO and O2.- between ex vivo and in vitro system. Together with the previous reports, these facts suggested that the mechanisms by which NO and O2.- probably from vascular constituent cells inhibit mitochondrial respiration function of isolated perfused rat lung may not be simply due to their direct reactions with mitochondrial electron transport chain components, but may rely on the formation of peroxynitrite, and/or peroxynitrite-derived oxidants.

Animals↗
PubMed1996

Pituitary adenylate cyclase-activating polypeptide induces gene expression of the catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine beta hydroxylase, through 3',5'-cyclic adenosine monophosphate- and protein kinase C-dependent mechanisms in cultured porcine adrenal medullary chromaffin cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP)i a potent stimulant of catecholamine secretion, increased catecholamine production in cultured porcine adrenal medullary chromaffin cells. PACAP induced dose-and time-dependent increases in mRNAs for the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), with maximal 6- and 4-fold increases occurring at 8-16 h, respectively. The half-maximally and maximally effective PACAP concentrations for stimulation of TH and DBH gene expression were 0.5 and 3 nM, respectively. The TH protein level also showed an increase over the unstimulated basal level at 16-24 h in PACAP-stimulate cells. We previously demonstrated that PACAP activates both phospholipase C and adenylate cyclase in adrenal medullary cells. Addition of forskolin alone induced increases in mRNA expression of both TH and DBH. The phosphodiesterase inhibitor 3- isobutyl-1-methylxanthine potentiated the induction of TH and DBH mRNAs by PACAP. Addition of the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) also caused increases in TH and DBH mRNA levels. In protein kinase C-downregulated cells pretreated with PMA for 24 h, the stimulatory effect of PACAP on TH and DBH gene expression was diminished. These results suggest that cAMP and protein kinase C mediate the PACAP-induced TH and DBH gene expression. Removal of extracellular Ca2+ with EGTA enhanced the PACAP-induced increases in both cellular cAMP and mRNA levels of TH and DBH, suggesting that Ca2+ has an inhibitory effect on the induction of TH and DBH mRNAs. In conclusion, the present study indicates that PACAP coordinately upregulates the gene expression of both TH and DBH by activating the cAMP and protein kinase C signaling pathways, leading to simulation of cate-cholamine synthesis, while Ca2+ negatively regulates TH and DBH gene expression in porcine adrenal medullary cells.

Adrenal Medulla↗
PubMed1996

1H-magnetic resonance spectroscopic observation of cultured malignant cells pharmacologically induced to different phenotypes.

RATIONALE AND OBJECTIVES: We evaluated the 1H nuclear magnetic resonance spectra of malignant cells after the administration of drugs that cause morphologic changes. METHODS: 1H spectra of a human lung adenocarcinoma cell line cultured with interferon gamma, dexamethasone, or sodium butyrate were obtained. The peaks were assigned by two-dimensional homonuclear Hartmann-Hahn spectroscopy spectra of the cells and their perchloric acid extracts. Differential spectra were used to evaluate relative changes in the peaks. RESULTS: In the control culture, choline/phosphocholine peaks were increased in the cell-growth phase, and the 1.26-ppm peak was increased in the confluent state. Treatment by interferon gamma and dexamethasone induced reproducible changes in the peaks of differential spectra corresponding to 1.26 ppm, choline/phosphocholine, and glutamate/glutamine. Dexamethasone treatment broadened lipid peaks. Changes after treatment with sodium butyrate were obscure. Microscopically, cells were induced to morphologically different phenotypes by each drug. CONCLUSION: Cells induced to exhibit morphologically different phenotypes present different 1H spectra.

Adenocarcinoma↗
PubMed1996

Effect of probucol, an oral hypocholesterolaemic agent, on acute tobacco smoke inhalation in rats.

1. We hypothesized that probucol, an oral hypocholesterolaemic agent, can suppress the oxidant stress induced by acute tobacco smoke inhalation in rats. We determined lung tissue glutathione (reduced and oxidized), lipid peroxide, tocopherol and plasma elastase inhibitory capacity, ferroxidase activity and lipid peroxide in rats after inhalation of tobacco smoke. 2. Rats treated with the probucol diet for 3 days or 4 weeks equally showed no suppression of plasma elastase inhibitory capacity and ferroxidase activity compared with control rats after acute tobacco smoke inhalation, although both animals treated with probucol for 3 days or 4 weeks had pharmacologically effective concentrations of probucol to lower plasma cholesterol but plasma cholesterol in rats treated with probucol for 3 days was still in the normal range. 3. Probucol treatment for 4 weeks lessened tobacco smoke-induced suppression of lung tissue glutathione, attenuated tobacco smoke-induced increases in lung tissue lipid peroxide and did not alter lung tissue tocopherol compared with control (lungs). 4. These findings demonstrate that probucol, via its antioxidant ability, confers a protective effect on lung exposed to acute tobacco smoke inhalation.

Animals↗
PubMed1996

Long-term alcohol intake enhances ADP-ribosylation of the multifunctional enzyme, phosphoglucomutase, in rat liver.

Adenosine diphosphate (ADP)-ribosylation is a posttranslational protein modification that, in turn, alters several regulatory proteins in mammalian cells. We demonstrated that long-term alcohol intake enhanced the ADP-ribosylation of a 58-kd protein in rat liver plasma membranes. To assess the biological significance of this phenomenon, we partially purified the 58-kd acceptor protein from solubilized rat liver homogenates by two sequential preparative high-pressure liquid chromatographies. Microsequencing revealed that it was phosphoglucomutase (PGM) (EC 5,4,2,2). This enzyme underwent negligible auto ADP-ribosylation, but the ADP-ribosylation was remarkably increased by adding rat liver plasma membranes. The extent of the increase was greater in alcohol-fed rats than in pair-fed controls, suggesting enhanced enzyme activities toward ADP-ribosylation of PGM after chronic alcohol consumption. Several important enzymes are ADP-ribosylated, after which their activities are modified. The results of this study showed that PGM is a novel substrate for ADP-ribosylation in the liver and that the ADP-ribosylation is increased after chronic alcohol consumption. In view of the variety of roles of PGM in the liver (carbohydrate metabolism and Ca2+ homeostasis), specific roles of this modification in terms of the effects of alcohol on hepatocytes may deserve further investigation.

Adenosine Diphosphate Ribose↗
PubMed1996

Effects of adenine nucleotide analogues on myocardial dysfunction during reperfusion after ischemia in dogs.

We examined effects of adenine nucleotide on ischemic myocardial stunning in dogs. Pentobarbitalanesthetized open-chest dogs were subjected to 20-min ligation of the left anterior descending coronary artery (LAD), followed by reperfusion for 30 min. Either saline, 5 mM 8-bromo-5'-AMP (tributyryl-AMP), or 30 mM N6, 2', 3'-tributyryl-5'-AMP (tributyryl-AMP), 5 mM 5-amino-4-imidazole carboxamide riboside (AICAr) as a positive reference, was infused at 0.1 ml/kg/min in the left femoral vein throughout the experiment. The myocardial contractile function was measured by ultrasonometry. The tissue levels of high-energy phosphates in the reperfused heart were determined. Myocardial contractile function assessed by % segment shortening (%SS) in the saline-infused group decreased during ischemia and returned toward the preischemic level during reperfusion but incompletely. A significant improvement in the %SS during reperfusion was observed in the 8-bromo-AMP- and AICAr-infused groups but not in the tributyryl-AMP-infused group. The magnitude of the protective effect of the drugs on myocardial contractility during reperfusion was 8-bromo-AMP > AICAr > tributyryl-AMP = saline. Only in the 8-bromo-AMP-infused group were the levels of ATP, ADP, and total adenine nucleotides in the reperfused heart significantly higher than those in the saline-infused group. The present result indicates that 8-bromo-AMP improves the ability of the heart to recover from ischemia and reperfusion associated with a significant restoration of ATP.

8-Bromo Cyclic Adenosine Monophosphate↗