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Biomedical subjects

I Maeda

Publications and source records attributed to I Maeda.

At least 37 records · Page 2Linked to original sources
PubMed1998

Broad spectrum and mode of action of an antibiotic produced by Scytonema sp. TISTR 8208 in a seaweed-type bioreactor.

A photobioreactor was constructed using anchored polyurethane foam strips (1 x 1 x 40 cm) fixed onto a stainless-steel ring to prevent flotation, as a biomass support material (BSM). This type of reactor was named a seaweed-type bioreactor. A filamentous cyanobacterium, Scytonema sp. TISTR 8208, which produces a novel cyclic dodecapeptide antibiotic, was immobilized in seaweed-type photobioreactor and cultivated with air containing 5% CO2 sparged at a gas flow rate of 250 mL/min under illumination at a light intensity of 200 mmol photon m-2 s-1. The antibiotic produced in the seaweed-type photobioreactor was purified by HPLC and examined regarding its spectrum and mode of action. The antibiotic effectively inhibited the growth of Gram-positive bacteria, pathogenic yeasts, and filamentous fungi, but it had only a weak effect on Gram-negative bacteria. Scanning electron micrograph analysis showed that the most characteristic change was swelling of the cells after exposure to the antibiotic. The antibiotic seems to alter the conformation of the microbial cell membrane, thereby changing its permeability, leading to osmotic shock.

Anti-Bacterial Agents↗
PubMed1997

Pharmacokinetics of adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation.

We investigated the pharmacokinetics of cytotoxic anticancer agents administered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) or a laparotomy and total hepatectomy under venovenous bypass (anhepatic group, n = 12). Each dog received a bolus intravenous injection of either Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urine concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the plasma Adriamycin concentrations remained persistently higher in the anhepatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group (P < 0.01 vs controls). The renal clearance values did not significantly differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepatic group than in the controls. In a second set of experiments with cisplatin, the plasma platinum concentrations did not significantly differ between the two groups throughout the time course. However, the renal clearance of platinum in the anhepatic dogs showed a fourfold increase compared with that in the controls (P < 0.01). These pharmacokinetic data suggest that Adriamycin carries the risk of increased systemic toxicities, while cisplatin may be associated with increased renal toxicity when administered during the anhepatic period of liver transplantation.

Animals↗
PubMed1997

Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors.

BACKGROUND: A single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique. PATIENTS AND METHODS: Sixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter. RESULTS: All patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P < 0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P < 0.01). CONCLUSIONS: The single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Aged↗
PubMed1996

Pharmacokinetics of intravenous adriamycin for anhepatic chemotherapy during liver transplantation.

Frequent recurrence of hepatocellular carcinoma after liver transplantation indicates the necessity to eliminate patients with advanced disease and combine transplantation with some form of perioperative adjuvant chemotherapy. This study was undertaken to elucidate adriamycin pharmacokinetics for anhepatic chemotherapy during liver transplantation. beagles of both sexes were allocated into two groups, controls (n = 4) and anhepatic animals with total hepatectomy under venovenous bypass (n = 5). In both groups, adriamycin was administered in 1 min at a dose of 1 mg/kg through the left antecubital vein and peripheral blood was obtained at intervals for up to 2 h to determine the plasma adriamycin levels. The animals were then sacrificed to determine tissue adriamycin levels in the liver, kidney, heart, lung, and skeletal muscle. Plasma adriamycin levels in anhepatic animals were significantly higher than those in controls at all measured time points after 10 min, resulting in a 50% reduction of the mean total body clearance of adriamycin compared with controls (P < 0.01). However, there was no statistically significant difference in adriamycin levels between the two groups for all measured tissues except for the liver. Despite the complete lack of hepatic function, anhepatic animals showed only a 50% reduction in total body clearance of adriamycin compared with normal controls, probably due to compensatory excretion from other organs such as the kidney. These results suggest that systemic chemotherapy with the standard dose of adriamycin may be tolerable during the anhepatic period of liver transplantation with enhanced tumoricidal effects on micrometastases.

Animals↗
PubMed1996

A novel paper cuff for vascular reconstruction in canine liver transplantation.

A new, simple method of producing optimal cuffs using thin paper and then setting it in resin for vascular reconstruction in canine liver transplantation is herein described. Thin Paper was cut into a paper tape strip. By fixing both ends of this paper tape, a cylinder paper core of any desired size could thus be obtained. The paper core was immersed into a two-liquid mixture-type resin, removed, and left to harden. The paper cuffs (0.2 mm or less in thickness) were then used for anastomoses of the portal vein and the infrahepatic inferior vena cava in a series of 10 consecutive canine liver transplantations. Out of 10 animals, 8 survived for more than 5 days. The vascular patency in these 8 animals at the cuff anastomotic sites was 100% at postmortem. We therefore conclude that this paper cuff appears to be useful for various types of experimental liver transplantations in large animals.

Anastomosis, Surgical↗
PubMed1996

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases.

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100-120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5-15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia < 2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intra-arterial chemotherapy in patients with unresectable hepatic tumors.

Adult↗
PubMed1996

Chymotrypsin inhibition induced by side chain-side chain intramolecular CH/pi interaction in D-Thr-L-Phe benzylamide.

The dipeptide benzyl amide H-D-Thr-Phe-NH-CH2-C6H5 was found to inhibit chymotrypsin strongly (K1 = 4.5 x 10(-6) M) in a competitive manner. When a series of phenyl amides H-D-Thr-Phe-NH-(CH2)n-C6H5 (n = 0-4) were tested, inhibitory potency peaked at n = 1 (benzyl amide). Incorporation of a methyl group into the benzyl methylene resulted in formation of stereoisomers, H-D-Thr-Phe-NH-(R or S)-CH(CH3)-C6H5, with considerably different inhibitory potencies. The R-isomer was as active as the benzyl amide, while the S-isomer was about 30-fold less active than the benzyl amide. Furthermore, when a fluorine atom was introduced into the para-position of the amide-benzyl group, the resulting H-D-Thr-Phe-NH-CH2-C6H4(p-F) showed considerably enhanced inhibitory activity (about 5-fold, K1 = 9.1 x 10(-7) M). In conformational analysis by 400 mHz 1H-NMR, all dipeptides having D-Thr-Phe backbone structure showed large upfield shifts of D-Thr-beta OH (shifts in ppm, 0.09-0.17), D-Thr-beta CH (0.23-0.32), and D-Thr-gamma CH3 (0.38-0.53), indicating the presence of shielding effects from the benzene ring. In addition, NOE enhancements between the D-Thr-gamma CH3 and Phe-phenyl groups were evidenced by measurements of two-dimensional NOESY spectra and NOE difference spectra. These observations demonstrated the spatial proximity of these side chains, which is due to side chain-side chain CH/pi interaction. All these results support the idea that the amide-benzyl group binds at the chymotrypsin S1 site, while the hydrophobic core with CH/pi interaction binds at the S2 or S1' site.

Chymotrypsin↗
PubMed1996

Biosynthesis of Poly(3-Hydroxyalkanoic Acid) Copolymer from CO(inf2) in Pseudomonas acidophila through Introduction of the DNA Fragment Responsible for Chemolithoautotrophic Growth of Alcaligenes hydrogenophilus.

Pseudomonas acidophila is a bacterial strain producing a poly(3-hydroxyalkanoic acid) (PHA) copolymer from low-molecular-weight organic compounds such as formate and acetate. The genes responsible for PHA production were cloned in cosmid pIK7 containing a 14.8-kb HindIII fragment of P. acidophila DNA. With the aim of developing a means of producing a PHA copolymer from CO(inf2), cosmid pIK7 was introduced into a polymer-negative mutant of the chemolithoautotrophic bacterium Alcaligenes eutrophus PHB(sup-)4. However, the recombinant strain produced a homopolymer of 3-hydroxybutyric acid (polyhydroxybutyric acid) from CO(inf2). Since it was thought that the composition of the accumulated polymer might depend not on the PHA biosynthetic genes but on the metabolism of the host strain, a recombinant plasmid, pFUS, containing the genes for chemolithoautotrophic growth of the hydrogen-oxidizing bacterium A. hydrogenophilus was introduced into P. acidophila by conjugation. The recombinant plasmid pFUS was stably maintained in P. acidophila in the absence of chemolithoautotrophic or antibiotic selection. This pFUS-harboring strain possessed the ability to grow under a gas mixture of H(inf2), O(inf2), and CO(inf2) in a mineral salts medium, and PHA copolymer accumulation was confirmed by nuclear magnetic resonance spectral analysis. A gas chromatogram obtained by gas chromatography-mass spectrometry showed the composition of the polymer to be 52.8% 3-hydroxybutyrate, 41.1% 3-hydroxyoctanoate, and 6.1% 3-hydroxydecanoate. This is the first report of the production of a PHA copolymer from CO(inf2) as sole carbon source.

Journal Article↗
PubMed1996

Purification and characterization of a cellulase from the giant snail Achatina fulica.

A cellulase with activity as a cellobiohydrolase [EC3.2.1.91] was purified from the intestinal juice of the giant snail Achatina fulica. The enzyme (M(r) = about 23,000, and pI = about 5.3) also had a weak beta-glucosidase activity. The amino acid sequence of the N-terminal 20 amino acids was analyzed, and no similarity was noted for sequences of other known cellobiohydrolases.

Amino Acid Sequence↗
PubMed1996

[Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion].

It is difficult to administer an effective dose of cyclosporin A (CsA), a potent inhibitor of P-glycoprotein, to prevent multiple drug resistance due to its side effect. We herein evaluated the efficacy of concomitant use of this agent and complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 4), intraarterial infusion of only adriamycin (ADM) and group II (n = 4), intraarterial infusion of CsA and ADM. In both groups, ADM was intraarterially administered for 10 minutes under HVI.CHP. In addition, in group II, CsA infusion (0.3 mg/min.kg) was initiated 20 min prior to the start of ADM infusion and maintained for 30 min. The AUC (micrograms.min/ml) of ADM were 21.2 +/- 8.6 (mean +/- SD) and 28.4 +/- 10.3 in groups I and II, respectively, at prefilter (hepatic venous level) and 8.1 +/- 4.6 and 4.8 +/- 3.8, respectively, at postfilter, showing an effective drug elimination in both groups. The Cmax (micrograms/ml) were 14.1 +/- 2.2 at prefilter, 2.4 +/- 0.5 at postfilter, and 3.4 +/- 1.2 in systemic level. These results indicated that HVI.CHP allowed the high-dose CsA infusion required for P-gp inhibition in the liver and could reduce extraregional CsA leakage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[The effect of high-dose intraarterial chemotherapy with percutaneous hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) for unresectable multiple hepatocellular carcinoma--comparison with other therapeutic modalities].

We evaluated the therapeutic effect of HVI.CHP in 11 patients with Stage III and IVA multiple hepatocellular carcinoma (group H) in comparison with conventional intraarterial chemotherapy (group S, 12 patients) and transarterial embolization (TAE; group T, 15 patients). The patients in each group had the same background as group H in terms of liver function tests. The Vp3 positive rates in group H (37%) and group S (47%) were significantly higher than group T (0%). One-year survival rates of groups H, S and T were 63. 6%, 8.3% and 46.7%, respectively, and 2-year survival rates were 63.6%, 0% and 20%, respectively. A significant difference was seen between the survival curves of groups H and S (p < 0.01), whereas no significant differences were detected between those of groups H and T. The survival rates for stage IVA patients in groups H, S and T were 55.6%, 10% and 40%, respectively, for 1 year and 55.6%, 0% and 10%, respectively, for 2 years. The difference of survival curves between Stage IVA patients of each group was analogous to those between overall patients of each group. Although 4 patients with Vp3 were included in group H but none in group T, the survival rates of group H were rather higher than in group T at 2 years. These data suggest that HVI.CHP could be the treatment of choice for unresectable multiple hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Evaluation of a single catheter technique for percutaneous isolated liver perfusion].

We have established a single catheter technique of percutaneous isolated liver perfusion using a 4-lumen-2-balloon (4L - 2B) catheter for treatment of unresectable malignant liver tumors. Herein reported are the technique, safety and pharmacokinetics of the system in comparison with the original double-balloon technique. This study included 19 patients with malignant liver tumors treated by adriamycin at a dose of 100 mg/m2. Seven patients had the double-balloon technique (group D), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other 12 patients had single catheter technique (group S). In group S, hepatic effluent was solely isolated and directed to CHP filters. All patients except for one in group S showed good hemodynamic stability. The hepatic venous flow rate of group S was significantly higher than in group D (p < 0.05). Although the mean area under the time concentration curve at systemic serum was significantly lower in group S compared to group D, the rate of side effects was similar in both groups. A 4L. 2B single catheter allowed safe and repeated percutaneous isolated liver perfusion for technical simplification of the treatment.

Aged↗
PubMed1996

[A case of advanced hepatoma cured by repeated percutaneous isolated liver perfusion using hepatic venous isolation and charcoal hemoperfusion].

We have reported the treatment results of percutaneous isolated liver perfusion using hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) for unresectable liver cancers. This is a case of multiple advanced hepatoma cured completely by repeated per cutaneous isolated liver perfusion. The patient was a 58-year-old woman who was referred to our hospital for a hepatic tumor detected by abdominal computed tomograpy (CT). On admission, she showed HBs antigen positive, mild anemia and liver dysfunction, and elevation of tumor markers. Abdominal CT demonstrated nodular tumors in segment 4. In addition, hepatic angiography additionally revealed multiple bilobar metastases. We treated this case with high-dose intraarterial adriamycin (150 mg/body) using HVI.CHP. There after, the patient received intermittent intraarterial low-dose epirubicin infusions (30 mg/body, 5 times) via an implantable catheter system. Furthermore, she was given a second high-dose of adriamycin (130 mg/body) under HVI.CHP 7 months after the first treatment. Despite repeated high-dose treatments, she had no severe side effects. The levels of tumor markers, including AFP and PIVKA-II, decreased to normal range, and all tumor nodules have disappeared in abdominal CT studies at present, 20 months after the initial treatment. In conclusion, our experience suggests that advanced hepatoma with multiple bilobar lesions, as in this case, would be cured by repeated percutaneous isolated liver perfusion using HVI.CHP.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[A case of advanced cholangiocellular carcinoma treated successfully by percutaneous isolated liver perfusion with cisplatin].

Herein reported is a case with unresectable intrahepatic cholangiocellular carcinoma (CCC) treated successfully with high-dose cisplatin infusion under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). The patient was a 43-year-old woman, who was investigated for liver dysfunction and subsequently referred to our institution with a diagnosis of unresectable intrahepatic CCC. We gave this patient a total of 2 treatments of percutaneous isolated liver perfusion with HVI.CHP (a total dose of cisplatin, 400 mg and adriamycin 30 mg). Although she had a slight elevation of serum GOT levels, leukopenia and renal dysfunction did not occur throughout the posttreatment course. The level of DUPAN-2 after the first treatment showed a marked reduction to 910 U/ml, from a pretreatment level of 2,700 U/ml. Abdominal CT scan also demonstrated a remarkable regression of liver tumors (PR: volume reduction, 76%). In conclusion, in percutaneous isolated liver perfusion using HVI.CHP, we have safely accomplished a dose intensification of intraarterial cisplatin. The treatment resulted in a marked tumor regression. Therefore, we consider that this method offers an effective therapeutic option for unresectable CCC.

Adult↗
PubMed1995

Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation.

The minimum graft volume still remains unclear in reduced-size liver transplantation (RLT). This study reports the improved survival of canine RLT using a quarter graft with the aid of a portahepatic vein shunt (PHVS). In beagles, the donor liver was reduced to the right lateral and caudate lobes (quarter graft) with or without provision of PHVS, and transplanted orthotopically in the recipient. The PHVS was established by an end-to-end anastomosis of the portal vein branch and the hepatic vein in the resected left lateral lobe. Liver chemistries including arterial blood ketone body ratio (AKBR) were serially measured during and after surgery. All seven animals with PHVS survived more than 3 days (mean +/- SD; 5.3 +/- 1.7 days), whereas all six without PHVS died within 3 days (1.8 +/- 0.8 days, P < 0.01). Portal vein pressures immediately after recirculation in animals with and without PHVS were 8.5 +/- 1.2 mmHg and 16.9 +/- 3.1 mmHg, respectively (P < 0.01). Regardless of the presence or absence of PHVS, AKBR dropped to a level lower than 0.7 during the anhepatic period and returned promptly to above 1.0 as early as 30 min after recirculation. Thereafter, the AKBR values in animals with PHVS remained higher than 1.0, whereas those in animals without PHVS showed a progressive decrease, showing a statistically significant difference between the two groups after 12 hr (P < 0.05). Graft function, as assessed by AKBR, was well correlated with survival and other liver chemistries. These results indicate that, in an extreme RLT, portal hypertension is a risk factor predisposing to graft failure, most likely by increasing microvascular injury after recirculation.

Animals↗
PubMed1995

Simultaneous determination of sulphamonomethoxine and its N4-acetyl metabolite in blood serum by high-performance liquid chromatography with direct injection.

A high-performance liquid chromatographic method with direct injection has been developed for the simultaneous determination of sulphamonomethoxine and its N4-acetyl metabolite in serum of animals and fish. A HISEP shielded hydrophobic-phase column (15 cm x 4.6 mm I.D.), a mobile phase of 0.05 M citric acid-0.2 M disodium hydrogenphosphate-acetonitrile (70:15:15, v/v), and ultraviolet detection at 265 nm were used. The standard calibration curves in serum of chicken, pig, cattle, rainbow trout and yellowtail were linear over the range 0.5-20 micrograms/ml. The recoveries of sulphamonomethoxine and its N4-acetyl metabolite from all serum samples determined at different concentrations (0.5, 2.0 and 10.0 micrograms/ml) were 93-103% and 90-103%, respectively. The lowest measurable sulphamonomethoxine and N4-acetyl metabolite concentrations were 0.04 and 0.1 microgram/ml, respectively, for all serum samples.

Acetylation↗