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Biomedical subjects

I Maeda

Publications and source records attributed to I Maeda.

At least 55 records · Page 3Linked to original sources
PubMed1995

[The effect of percutaneous hepatic venous isolation and charcoal hemoperfusion for high-dose chemotherapy for hepatoma].

We herein report the efficacy of percutaneous high-dose chemotherapy under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) in the treatment of hepatoma patients. This study included 23 patients with bilobar multiple intrahepatic metastases and 1 patient with high risk for recurrence after hepatectomy. All patients received adriamycin at doses ranging from 60-150 mg/m2 through the hepatic artery. Sixteen patients had HVI.CHP by the double-balloon technique, while a recent 8 patients had the single catheter technique using a 4L.2B catheter; 4 of these 8 patients had repeated treatment. Except for two early patients with hepatic arterial thrombosis and necrotizing pancreatitis, there was no lethal complication, and quality of life after treatment was remarkably improved in patients treated by the single catheter technique. Among 22 evaluable patients, 3 had CR and 11 had PR, yielding a response rate of 63%. Mean survival duration was prolonged to 13 months in responders, against only 5 months in nonresponders. In conclusion, HVI.CHP was highly effective for advanced hepatoma patients and the single catheter technique facilitated a repeated high-dose intraarterial chemotherapy, which may offer a possibility of complete remission even in highly advanced cases.

Carcinoma, Hepatocellular↗
PubMed1995

[Pharmacokinetic comparison of intraarterial and intraportal infusion of adriamycin in regional chemotherapy of the liver].

We investigated the adriamycin (ADR) pharmacokinetics following intraarterial and intraportal infusion under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). HVI.CHP was used to measure the first-pass amount of adriamycin through the liver and to reduce hepatic re-entry of the drug. Beagles underwent a 10-min ADR infusion (1 mg/kg) either through the hepatic artery (group I, n = 5) or the portal vein (group II, n = 5) under a 20-min HVI.CHP. During HVI.CHP, the hepatic venous flow rate and plasma ADR levels in prefilter (hepatic venous level), postfilter and peripheral blood were serially measured. Based on these measurements, the hepatic extraction ratio (HER) of ADR was calculated. Areas under the time-concentration curves of prefilter levels in groups I and II were 6.1 +/- 1.6 and 16.9 +/- 5.0 micrograms.min/ml, respectively, showing a significant difference between two groups (p < 0.01). On the contrary, HER of group I (81.2%) was significantly higher than that of group II (47.2%, p < 0.01). These results indicate that intraarterial infusion of ADR is superior to intraportal infusion in terms of local drug delivery to the liver and systemic drug toxicities.

Animals↗
PubMed1995

[Pharmacokinetic evaluation of complete infrarenal inferior vena caval isolation and charcoal hemoperfusion for intra-arterial chemotherapy of pelvic tumors].

Regional chemotherapy for malignant pelvic tumors is disappointing due to the poor tumor response and dose-limiting systemic toxicity. This study was designed to determine whether a novel venous isolation-charcoal hemoperfusion system could limit systemic exposure to chemotherapeutic agents after regional arterial infusion. Adriamycin (2 mg/kg) was continuously administered in the internal iliac arteries of beagles under complete isolation of the infrarenal inferior vena cava and extracorporeal charcoal hemoperfusion (IVCI.CHP). Control beagles received adriamycin at the same dosage without IVCI.CHP. Plasma adriamycin concentrations were measured in the left carotid artery (systemic level) at intervals of up to 40 minutes after the start of drug infusion. In animals with IVCI.CHP, the drug levels were also determined at the inlet and outlet of a CHP filter. The mean drug extraction ratios by the CHP filter averaged 88%. As a result, animals with IVCI.CHP showed a significant reduction in systemic drug levels at all measuring time points compared to controls. The peak systemic levels of adriamycin were 0.8 +/- 0.1 and 2.3 +/- 0.8 micrograms/ml, respectively, in IVCI.CHP and control animals (p < 0.01). IVCI.CHP accomplished a significant reduction in systemic exposure to adriamycin after iliac arterial infusion. This novel system will allow regional delivery of high-dose cytotoxic agents with little systemic toxicity for pelvic tumors.

Animals↗
PubMed1995

[A case of malignant fibrous histiocytoma treated with intraarterial chemotherapy under complete venous isolation and charcoal hemoperfusion].

Herein reported is a case with malignant fibrous histiocytoma (MFH) at the left elbow treated successfully with intraarterial chemotherapy under complete brachial venous isolation and charcoal hemoperfusion (BVI-CHP). A 56-year-old man was admitted to our institution because of local recurrence at the left elbow 6 months after extended local resection combined with systemic chemotherapy. We treated the patient with a 15-min intraarterial infusion of adriamycin (100 mg/body) and cisplatin (30 mg/body) under a concomitant 30-min BVI-CHP. Two weeks after the first treatment, he received a repeated intraarterial infusion of adriamycin (80 mg/body) and cisplatin (50 mg/body) under BVI-CHP. The tumor became necrotic one week after the first treatment, resulting in 60% reduction in tumor diameter. In addition, angiography demonstrated a remarkable shrinkage of the tumor stain. Despite repeated intraarterial high-dose infusions of chemotherapeutic agents, systemic toxicities, such as leukopenia, nausea/vomiting and alopecia, were not observed. These results indicate that this approach offers a novel therapeutic option for malignant tumors in the extremities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Idea and practice with the systematization of clinical laboratory in the Central Laboratory, Osaka University Hospital].

On 1 September 1993, we left our old hospital and moved to our brand new establishment, and at that time we adopted the order-entry and reporting system. In this paper we report on our new laboratory computer system that has been developed to manage a lot of information and to analyze rapidly many test tubes (4000 samples per day) and to elevate the service for our patients. We developed the automated clinical laboratory system and this new system was named as the Clinical Laboratory Supervised System (CLASSY). We used the NEC system 3500 Model 10, NEC N5200 Model 03 sx and NEC PC9821 Ae as a laboratory host computer, an interface unit and a terminal for routine work, respectively. CLASSY covers the automated analysis not only for clinical chemistry, but also for hematology, urinalysis and microbiology. As the ordering and reporting system is applied to the hospital information system, order information for clinical test is transferred to our laboratory host computer when the bar-code label is printed out from the automatic bar-code labeller. Then it is transferred from the laboratory host computer to some subsystems or automatically to an analyzer through the interface units or modems.

Clinical Laboratory Information Systems↗
PubMed1993

Water-soluble chymotrypsin specific inhibitors containing arginine.

In an attempt to develop water-soluble, potent inhibitors for chymotrypsin, structurally rigid dipeptides containing arginine were designed and synthesized. The dipeptide H-D-Arg-Phe-NHBzl inhibited chymotrypsin very strongly (Ki = 5.9 microM). The dipeptide with the inverse sequence, H-D-Phe-Arg-NHBzl, was also a moderate inhibitor for chymotrypsin with Ki of 240 microM. In spite of the presence of arginine in these dipeptides, they inhibited trypsin only weakly, indicating that they are highly specific for chymotrypsin. High resolution 1H-NMR (400-MHz) indicated that these dipeptides can make a strong intramolecular hydrophobic interaction between Arg-beta, gamma, delta-methylenes and Phe-phenyl, producing a rigid hydrophobic core which interacts with the chymotrypsin S2 site. Since these dipeptides are easily soluble in water, they are regarded as the sophisticated and effective inhibitors for chymotrypsin.

Amino Acid Sequence↗
PubMed1993

Effects of ML-9 on insulin stimulation of glucose transport in 3T3-L1 adipocytes.

Treatment of 3T3-L1 adipocytes with insulin resulted in activation of 2-deoxyglucose transport activity and translocation of glucose transporters (GLUT4 and GLUT1) from the cytoplasmic space to the plasma membrane. ML-9 (a myosin light chain kinase inhibitor) inhibited insulin stimulation of 2-deoxyglucose transport activity by 80% at 100 microM (IC50 = 27 microM) without affecting 2-deoxyglucose transport activity in the basal state. The inhibition was independent of extracellular Ca2+ concentration and almost fully reversible at 40 microM ML-9. ML-9 did not inhibit insulin-stimulated tyrosine phosphorylation of 95-kDa protein in the wheat germ agglutinin-purified preparation and of 95- and 160-kDa proteins in intact cells. However, ML-9 inhibited insulin-induced translocation of both GLUT4 and GLUT1 in a dose-dependent manner. The dose-response curves were similar to those observed for the inhibition of insulin stimulation of 2-deoxyglucose transport activity. Neither insulin nor ML-9 affected the phosphorylation state of both heavy and light chains of myosin. Therefore, it seems likely that ML-9 inhibits the insulin-induced translocation of glucose transporters at a step beyond the insulin receptor kinase activity by a mechanism different from that affecting phosphorylation of the myosin light chain. Phosphorylating activity of microtubule-associated protein 2 and myelin basic protein was stimulated by insulin, and this stimulation was not affected by ML-9. ML-9, however, inhibited the phosphorylating activity in vitro and insulin stimulation of the phosphorylating activity of ribosomal protein S6 in intact cells in a dose-dependent manner similar to that observed for the inhibition of insulin stimulation of glucose transport. These results suggest that mitogen-activated protein kinase may be one of the constituents in intracellular insulin signaling to the glucose transport system.

3T3 Cells↗
PubMed1993

Chymotrypsin inhibitory conformation of dipeptides constructed by side chain-side chain hydrophobic interactions.

A complete series of configurational isomers (L-L, L-D, D-L and D-D) of a dipeptide Leu-Phe benzyl ester have been synthesized and assayed for chymotrypsin. In the conformational analysis by 400 MHz 1H NMR, the L-D and D-L isomers, but not the L-L and D-D isomers, showed fairly large upfield shifts (0.2-0.4 ppm) of Leu-beta CH2 and gamma CH proton signals, indicating the presence of shielding effects from the benzene ring. In addition to distinct signal splitting of Phe-beta CH2, the NOE enhancement observed between Leu-delta CH3 and Phe-phenyl groups revealed that these groups are in close proximity. These data indicated that L-D and D-L isomers form a hydrophobic core between side chains of adjacent Leu and Phe residues. When the dipeptides were examined for inhibition of chymotrypsin using Ac-Tyr-OEt as a substrate, the L-L isomer showed no inhibition, itself becoming a substrate. However, the other three isomers inhibited chymotrypsin in a competitive manner, and the D-L isomer was strongest with Ki of 2.2 x 10(-5) M. It was found that the D-L isomer was only slowly hydrolysed but the L(or D)-D isomer was not. H-D-Phe-L-Leu-OBzl with the inverse sequence of H-D-Leu-L-Phe-OBzl inhibited chymotrypsin more strongly (Ki = 6.3 x 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Chymotrypsin↗
PubMed1992

Insulin resistance in Werner's syndrome.

Insulin resistance in Werner's syndrome (WS) was studied using the glucose clamp technique, and compared with physiologically aged and young subjects. Fasting immuno-reactive insulin (IRI) was increased in patients with Werner's syndrome compared with aged and young subjects. Metabolic clearance rate (MCR) of glucose was decreased in the aged and WS. A rightward shift of the dose-response curves of insulin and MCR of glucose was observed in the aged and WS with a more pronounced shift in the latter. MCR of insulin was also decreased in WS. [125I]insulin binding to erythrocytes was similar in the three groups. These results suggest that insulin resistance associated with WS is due to a post-binding defect manifested by a rightward shift of the dose-response curve of insulin-induced glucose disposal and a decrease in insulin clearance rate.

Adult↗
PubMed1992

Monoclonal antibodies possibly recognize conformational changes in the human erythrocyte glucose transporter.

Two monoclonal antibodies (MAG17 and MAG20) were raised against the human erythrocyte glucose transporter, which was purified on an immunoaffinity column using a polyclonal antibody to the C-terminal peptide (residues 477-492) of the glucose transporter of HepG2 cells. To obtain antibodies which recognize the native glucose transporter integrated in the membrane, hybridomas were screened both by e.l.i.s.a. with purified glucose transporter and by dot-blotting with erythrocyte membranes. The antibodies immunoprecipitated D-glucose-inhibitable [3H]cytochalasin B-photoaffinity-labelled glucose transporters, but did not recognize the transporter on Western blotting. The presence of the C-terminal peptide did not inhibit the binding of these antibodies to the glucose transporter, suggesting that the antibodies recognized sites different from the transporter C-terminus. D-Glucose (0.1-100 microM) inhibited the binding of MAG17 and MAG20 to the transporter by 50%, indicating that the conformation of the epitopes was altered allosterically by D-glucose. Cytochalasin B inhibited the binding of MAG17 to the transporter, but enhanced the binding of MAG20 at low concentrations (less than 0.02 microM). These data suggest that the glucose transporter has high- and low-affinity binding sites for D-glucose and cytochalasin B, and that binding of D-glucose and cytochalasin B induces conformational changes in the transporter. Monoclonal antibodies which recognize the tertiary structure of the glucose transporter can be used for investigating its function and structure when integrated in the membrane.

Amino Acid Sequence↗
PubMed1992

[An electron microscopic study on osteoblastoma--ultrastructure and fine localization of alkaline phosphatase].

Three cases of osteoblastoma were studied by electron microscopy. They included two cases of conventional osteoblastoma and one case of aggressive osteoblastoma. In conventional osteoblastoma, ultrastructural features and location of alkaline phosphatase activity of the osteoblast-like cell were similar to those of normal osteoblast. On the other hand, aggressive osteoblastoma cell (case 3) showed different structure from those of a normal osteoblast; the nucleus of the tumor cell showed irregular surface with a small degree of heterochromatin, and poorly developed cytoplasmic organellae. Cytochemically, alkaline phosphatase activity was noted not only on the cytoplasmic membrane, but on the abundant vesicles in the cytoplasm. From these findings we conclude that the aggressive osteoblastoma cells are more immature in morphology and show increased synthesis of alkaline phosphatase.

Adolescent↗
PubMed1991

Regulation of glucose transporter synthesis in cultured human skin fibroblasts.

The present study was designed to see the effects of glucose on glucose transporter expression and glucose transport activity using cultured human skin fibroblasts. When the cells were incubated with various concentrations of glucose (11.1-44.4 mM), no differences were found in the HepG2 glucose transporter mRNA, protein levels and basal and insulin-stimulated 2-deoxyglucose uptake. Glucose deprivation, however, resulted in approximately 4-fold increases in the mRNA and 3-fold increases in the protein and the basal 2-deoxyglucose uptake. Chronic exposure to insulin increased the glucose transporter protein levels to similar degrees in the cells incubated with 11.1, 22.2 and 44.4 mM glucose accompanied by increases in the glucose transport activity. Effects of insulin on the glucose transporter mRNA and protein levels, however, were not evident in the glucose-deprived cells. It is concluded that glucose transport activity correlates closely with HepG2 glucose transporter expression in cultured human fibroblasts and that glucose (11.1-44.4 mM) does not affect the glucose transporter expression and glucose transport activity.

Blotting, Western↗
PubMed1991

Insulin-stimulated glucose uptake and fasting blood glucose.

Changes in insulin-stimulated glucose metabolism were studied in young and aged subjects, subjects with impaired glucose tolerance, and patients with NIDDM by means of the glucose clamp technique. The diabetic group includes obese and non-obese patients treated without insulin and non-obese patients treated with insulin. The glucose disposal rate (GDR) was decreased in aged subjects (5.8 +/- 0.4 mg/kg/min) compared with young controls (7.4 +/- 0.3 mg/kg/min). In patients with IGT, it was further decreased to 3.6 +/- 0.5 mg/kg/min, which was comparable to the rate in NIDDM without insulin treatment (3.3 +/- 0.4 mg/kg/min). There were no differences in the GDR between obese (3.0 +/- 0.3 mg/kg/min) and non-obese (3.4 +/- 0.6 mg/kg/min) diabetic patients. In insulin-treated diabetic patients, GDR ranged widely, but the mean value was partially normalized (5.2 +/- 0.9 mg/kg/min). In the diabetic group, no correlation was observed between fasting blood glucose and GDR. These results suggest that in the course of developing NIDDM, a decrease in insulin-stimulated glucose uptake precedes a rise in fasting blood glucose. Thus, as previously reported for Caucasian NIDDM patients, resistance to insulin-stimulated glucose uptake may be one of the basic defects in Japanese patients with NIDDM. The degree of glycemia, however, is not directly related to the magnitude of the defect in insulin action.

Adult↗