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Biomedical subjects

T Irie

Publications and source records attributed to T Irie.

At least 73 records · Page 4Linked to original sources
PubMed1999

Enhanced absorption of cyclosporin A by complexation with dimethyl-beta-cyclodextrin in bile duct-cannulated and -noncannulated rats.

The enhancing effects of dimethyl-beta-cyclodextrin (DM-beta-CyD) on the absorption of cyclosporin A (CsA) after oral administration to rats under bile duct-cannulated and -noncannulated conditions were investigated. The dissolution rate of CsA was markedly augmented by complexation with DM-beta-CyD. In a closed loop in situ study, DM-beta-CyD considerably increased the cumulative amounts of CsA in the mesenteric venous blood after injection of the aqueous CsA suspension into the small intestinal sac of rats. In addition, the cumulative amount ratio of M1, the dominant metabolite of CsA in rats, to CsA in the mesenteric venous blood for up to 40 min after the injection of the CsA-DM-beta-CyD suspension into the sac was lower than that of the CsA suspension alone. DM-beta-CyD inhibited the bioconversion of CsA in the small intestinal microsomes of rats. These results indicate that the bioconversion of CsA was abated by complexation with DM-beta-CyD. An in vivo study revealed that DM-beta-CyD increased the transfer of CsA to blood, not lymph, with low variability in the absorption after oral administration of the CsA suspension to rats. The variability of bioavailability of DM-beta-CyD complex was lower than that of Sandimmune, although the extent of bioavailability of DM-beta-CyD was only a little higher than that of Sandimmune. The bioavailability of CsA or its DM-beta-CyD complex was appreciably decreased by the cannulation of the bile duct of rats, and the extent of the lowering in the bioavailability in the presence of DM-beta-CyD was much less serious than that of CsA alone. The present results suggest that DM-beta-CyD is particularly useful in designing oral preparations of CsA with an enhanced bioavailability and a reduced variability in absorption.

Administration, Oral↗
PubMed1999

Does resection of small liver metastases from colorectal cancer improve survival of patients?

Because the size of metastases greatly affects their detection, we retrospectively investigated the influence of the size of liver metastases on survival after hepatic surgery. The subject group study consisted of 77 patients who underwent liver surgery for metastases from colorectal cancer. The survival rate after hepatic surgery was analysed using multivariate Cox's proportional hazards model with the following variables: (1) size of dominant metastases (Small: < 3 cm; Medium: > or = 3 cm and < 6 cm; Large: > or = 6 cm); (2) synchronous versus metachronous resection; (3) solitary versus multiple metastases. The size of dominant metastases (p = 0.035) and synchronous versus metachronous resection (p = 0.0009) were independently associated with survival after liver resection. No association was found, however, for solitary versus multiple metastases. The survival of the Large group was much poorer than that of the Small group (p = 0.0168) and that of the Medium group (p = 0.0205), with statistically significant differences. No statistically significant difference was seen between the Small and the Medium groups (p = 0.7963). This study showed that long-term survival following resection of metastases was much poorer when metastases were 6 cm or greater in diameter. With regard to metastases less than 6 cm in diameter, resection of the smallest of these (less than 3 cm) did not appear to improve survival.

Adult↗
PubMed1999

[Clinical outcomes in low grade follicular lymphoma].

Twenty-six patients with follicular small-cleaved lymphoma (FSCL) and 16 patients with follicular mixed lymphoma (FML) were treated at the Nichidai Itabashi Hospital between 1981 and 1995. The 5-year overall survival rate was 74.3% and 70.0% for the FSCL and FML patients, respectively. Of the patients with stage III-IV FSCL, 9 were assigned to a "watchful waiting" follow-up course and 13 were treated with a single alkylating agent or CHOP therapy. The 5-year failure-free survival rate was 66.7% and 33.0%, respectively. Of the patients with stage II-IV FML, 6 were treated with CHOP or MACOP-B protocol. The complete response rate for this group was only 33.3%, and none of the patients were in remission for more than 2 years. Histological transformation into diffuse aggressive lymphoma was observed in 7 patients, with the median time from diagnosis to transformation at 50 months. Three of those patients were successfully treated with intensive chemotherapy after transformation.

Adult↗
PubMed1999

Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson's disease and progressive supranuclear palsy.

We measured brain acetylcholinesterase activity in 16 patients with Parkinson's disease (PD), 12 patients with progressive supranuclear palsy (PSP), and 13 age-matched controls, using N-methyl-4-[11C]piperidyl acetate and positron emission tomography. Kinetic analysis was performed to calculate k3, an index of acetylcholinesterase activity. In PD patients, there was a significant reduction (-17%) of cerebral cortical k3 compared with normal controls, whereas there was only a nonsignificant reduction (-10%) of cortical k3 in PSP patients. However, there was a prominent reduction (-38%) of thalamic k3 in PSP patients compared with normal controls, whereas there was only a nonsignificant reduction (-13%) of thalamic k3 in PD patients. The results suggest that there is a loss of cholinergic innervation to the cerebral cortex in association with cholinergic innervation to the thalamus in PD, whereas there is a preferential loss of cholinergic innervation to the thalamus in PSP. When the thalamic to cerebral cortical k3 ratio was taken for each subject, PD and PSP were separated, suggesting that positron emission tomography measurement of acetylcholinesterase activity may be useful for differentiating the two similar disorders.

Acetylcholinesterase↗
PubMed1999

[Experimental study on intraperitoneal and intravenous administration of anti-tumor agents for liver metastasis].

Intraperitoneal chemotherapy has been the treatment for peritoneal seedings. Most of the anti-tumor agent administered intraperitoneally is absorbed from visceral peritoneum, gets into the portal vein system and reaches the liver. Theoretically, intraperitoneal administration of anti-tumor agents must show equivalent effects on the liver metastasis to portal vein infusion. We compared the efficacy of intraperitoneal and intravenous administration of 5-FU, CDDP and CPT-11, using colon 26 mouse liver metastasis model. Intraperitoneal administration of 5-FU or CPT-11 was statistically superior to intravenous administration to diminish the liver metastatic deposits. CDDP experiment did not show a statistical difference, but the superiority intraperitoneal administration was recognized. Intraperitoneal administration of anti-tumor agents is more effective for not only peritoneal seedings but also liver metastases than intravenous administration. Intraperitoneal chemotherapy might be an effective adjuvant chemotherapy for gastrointestinal malignancies.

Animals↗
PubMed1999

[Pharmaco-dynamic study of methotrexate (MTX) during intraperitoneal MTX/5-FU sequential therapy after gastric surgery].

A pharmaco dynamic study of Methotrexate (MTX) during intraperitoneal MTX/5-FU sequential therapy was carried out after gastric surgery. A comparative study of the route of MTX administration and its dose was also done. 1) Comparative study of the serum concentration of MTX between i.p. and i.v. administration revealed a similar MTX concentration except immediately after administration. 2) A comparative study of the serum concentration of MTX administered i.p. between patients with and without malignant ascites was conducted. Immediate elevation of the serum concentration of MTX was observed in patients without malignant ascites. On the other hand, the MTX concentration was slowly elevated and washed out in patients with malignant ascites. 3) The MTX concentration in the intraperitoneal fluid was compared between patient with and without malignant ascites. In patients without malignant ascites, MTX disappeared quickly from the intraperitoneal fluid. However, the MTX concentration lasted long in the malignant ascites cases. These results were similar with a low-dose MTX (30 mg/body) or moderate dose (100 mg/body). MTX/5-FU sequential i.p. therapy can thus be an effective treatment for patients after gastric surgery, though clearance of MTX was slow in cases with malignant ascites.

Combined Modality Therapy↗
PubMed1999

[Intrabiliary administration of doxorubicin for pancreaticobiliary cancer].

UNLABELLED: The effect and drug absorbtion of intrabiliary chemotherapy with Doxorubicin for pancreaticobiliary cancer with PTCD was investigated. Doxorubicin (DXR: 20 mg) was administered intrabiliary for 3 hours by PTCD catheter. Radiographic evaluation of the bile duct before and after chemotherapy and measurement of DXR concentration in the serum and bile were carried out. RESULTS: Intrabiliary administration of DXR was completed without any significant complications other than epigastric pain. Radiographic study of the bile duct of a patient with pancreatic cancer who could successfully complete DXR administration showed improvement of bile duct passage. The placement of biliary stent could be achieved. Concentration of DXR in the serum after administration was below the lowest determinable level while those in the bile maintained a considerably high concentration 4 hours after the administration. With negligible absorption from bile, intrabiliary chemotherapy with DXR was thought to be an acceptable palliative treatment for pancreaticobiliary cancer.

Aged↗
PubMed1999

[Patterns of initial treatment failure of esophageal cancer following radiotherapy].

Sixty patients with stage I-III esophageal squamous cell cancer treated by definitive radiotherapy (RT) were analyzed for patterns of treatment failure. Patients were treated by external RT alone (n = 45) or in combination with intraluminal RT (N = 15) when suitable, with prescribed total doses ranging from 59.4 to 104.4 Gy. Concurrent chemotherapy consisting of cisplatin and/or 5-fluorouracil was administered to 19 patients. The two-year actuarial survival rate and two-year disease-free survival rate were 29.5% and 18.3%, respectively. Two-year failure rates were 66.5%, 36.9%, and 3.8%, for the esophagus, lymph nodes, and other sites, respectively. Two-year esophageal failure rates for patients with T1-2 (n = 8), T3 (n = 30), and T4 disease (n = 22) were 14.3%, 64.7%, and 87.9%, respectively (p < 0.05). A multivariate analysis of esophageal failure with descriptive variables of T classification, tumor length, and performance of intraluminal RT revealed that only T classification was an independent factor (p = 0.021). Two-year lymph node failure rates were 24.8% and 33.6% for patients with N0 (n = 36) and N1 disease (n = 24), respectively (p = 0.0035). Lymph node failure in N0 patients was found exclusively outside the treatment field. These results suggest that inclusion of potential lymph node metastases in the radiation field could lessen the lymph node failure rate in T1-3N0M0 patients.

Aged↗
PubMed1999

[Merocyanine 540-mediated photodynamic therapy inhibits P-glycoprotein (P-gp) activity in adriamycin-resistant K562 cells].

The photosensitizing dye merocyanine 540 (MC540) has been used in preclinical models and in a phase I clinical trial in the U.S.A. for the extracorporeal purging of autologous bone marrow grafts contaminated with leukemia or lymphoma. In this communication, we report MC540-mediated photodynamic therapy (PDT) was effective in purging leukemic cells expressing P-gp. When K562 and K562/ADM were exposed to MC540 (15 micrograms/ml) and white light (145.8 kJ/m2), the concentration of K562 and K 562/ADR was reduced by 1.8 and 3.0 log, respectively. Using flow cytometry and confocal laser scan microscopy, MC540 and calcein-AM were bound intracellularly and effluxed by P-gp in K562/ADM. In K562/ADM, calcein-AM efflux was inhibited by P-gp modulator, cyclosporin A (5 microM) and verapamil (15 micrograms/ml). In contrast, MC540 efflux was inhibited by cyclosporin A but not verapamil. Furthermore, MC540-mediated PDT inhibited efflux of calcein-AM and MC540, and induced the accumulation of dyes in K562/ADM. We conclude that MC540 is a substrate of P-gp and that MC540-mediated PDT is useful for purging MDR cells through inhibition of P-gp activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

[Hemodynamics at hepatoarterial infusion of 5-FU in a chronic renal failure patient maintained by hemodialysis].

The authors studied the hemodynamics of 5-FU hepatoarterial infusion in a colorectal cancer patient with multiple liver metastases, who had chronic renal failure maintained by hemodialysis. Under weekly high dose 5-FU hepatoarterial infusion (1,000 mg/m2, 5 hours), on a non-dialysis day, serum 5-FU concentration was 1,090 ng/ml just after the 5 h infusion, 391 ng/ml at 15 min, 217 ng/ml at 30 min, 47 ng/ml at 60 min, and < 4 ng/ml at 120 min after infusion. On a dialysis day it was 1,500 ng/ml just after infusion, 41 ng/ml at 15 min, 5 ng/ml at 30 min, and < 4 ng/ml at 60 and 120 min after infusion. A control group (n = 4), who had liver metastases from colorectal cancers and normal renal functions, showed 5-FU serum concentration of 987 +/- 384 ng/ml just after infusion, 226 +/- 117 ng/ml at 15 min, 18.5 +/- 5.8 ng/ml at 30 min, < 4 ng/ml at 60 and 120 min after infusion. The serum 5-FU concentration of the patient was maintained higher on non-dialysis days, while it decreased more rapidly on dialysis days than that of the control group. There were no clinical complications due to the weekly high dose 5-FU hepatoarterial infusion. Under the treatment of continuous 5-FU hepatoarterial infusion (500 mg/day), the serum 5-FU concentration of this patient was kept under 115 ng/ml. After hemodialysis, the concentration decreased. The serum 5-FU concentration of the control group (n = 4) was under 66 ng/ml. There were no side effects under the protocol of continuous 5-FU hepatoarterial infusion. 5-FU hepatoarterial infusion for liver metastasis was a safe treatment for a renal failure patient with hemodialysis.

Aged↗
PubMed1998

The metabolic pathway of visual pigment chromophore formation in Drosophila melanogaster--all-trans (3S)-3-hydroxyretinal is formed from all-trans retinal via (3R)-3-hydroxyretinal in the dark.

Carotenoid-depleted fruit flies, Drosophila melanogaster, were reared on yeast/glucose medium containing lipid-depleted white corn grits and cholesterol. After rearing for more than a year, the yield of flies remained constant and the content of 3-hydroxyretinal in a head was three logarithmic units less than that of normal flies reared on medium containing yellow corn grits. When all-trans retinal was supplied as the sole source of retinoids, the flies formed and accumulated all-trans 3-hydroxyretinal in the dark. To examine the metabolic pathway to produce (3S)-3-hydroxyretinal in Drosophila, all-trans retinal was supplemented for two hours to carotenoid-depleted flies in the dark, and the subsequent changes in the composition of 3-hydroxyretinal enantiomers were analyzed using a chiral column on HPLC. The results indicated initial formation of (3R)-3-hydroxyretinal followed by isomerization into the 3S enantiomer. In another set of experiments, the membrane fraction was obtained from the head homogenate of retinoid-depleted flies and an in vitro assay of 3-hydroxyretinal formation from retinal was performed. The 3-hydroxyretinal produced was the 3R enantiomer, supporting the result obtained from the in vivo experiment whereby (3S)-3-hydroxyretinal is produced from retinal via (3R)-3-hydroxyretinal. Addition of NADPH enhanced 3-hydroxyretinal formation and the presence of carbon monoxide inhibited it, suggesting that hydroxylation at the C3 position of retinal occurred via the monooxygenase activity of cytochrome P-450.

Animals↗
PubMed1998

Chloride concentration in cultured hippocampal neurons increases during long-term exposure to ammonia through enhanced expression of an anion exchanger.

The effects of long-term exposure to ammonia on [Cl-]i in cultured hippocampal neurons were examined. Ammonia increased the [Cl-]i time- (>/=24 h) and concentration- (>/=2 mM) dependently, resulting in a depolarizing shift of the equilibrium potential of the GABAA receptor-Cl- channel opening (EGABA). Such an effect of ammonia was diminished by the inhibitors of Cl-/HCO3- exchangers, 0.1 mM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 0.1 mM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and a carbonic anhydrase inhibitor, 2 mM acetazolamide, but not by a Na+/K+/2Cl-cotransport inhibitor, 50 microM bumetanide, suggesting an enhanced Cl-/HCO3- exchange activity by ammonia. The ammonia-induced increase in [Cl-]i was also abolished by the inhibitors of protein kinase C (PKC), 0.1 microM calphostin C and 10 microM 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine dihydrochloride (H-7), and of transcription and de novo protein synthesis, 1 microM actinomycin D and 0.5 microg/ml cycloheximide, while a PKC activator, 0.1 h microM phorbor 12-myristate 13-acetate (PMA), increased the [Cl-]i. The mRNA level of the AE3 Cl-/HCO3- exchanger was increased by ammonia in a calphostin C- and H-7-sensitive manner. The AE3-like immunoreactivity was also increased by ammonia. These findings suggest that long-term exposure to ammonia increases the expression of AE3 through the activation of PKC, resulting in an increase in [Cl-]i in neurons and a reduction of inhibitory postsynaptic potentials.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Cloning and characterization of the gene encoding the iron-sulfur protein of succinate dehydrogenase from Pleurotus ostreatus.

Genomic and cDNA fragments encoding the iron-sulfur protein (Ip) subunit of dehydrogenase (EC 1.3.99.1) have been cloned from the edible basidiomycetous fungus, Pleurotus ostreatus. The gene is interrupted by five introns and is predicted to encode a polypeptide of 268 amino acid residues. Sequence comparison with the Ip subunit from other species identified three conserved cysteine-rich clusters. One of these contains a critical histidine residue implicated in carboxin sensitivity in the heterobasidiomycete Ustilago maydis.

Amino Acid Sequence↗
PubMed1998

Effects of protein kinase and phosphatase inhibitors on slow shortening of guinea pig cochlear outer hair cells.

The intracellular mechanisms of slow shortening in isolated guinea pig cochlear outer hair cells were investigated using inhibitors and/or an activator of protein kinases and protein phosphatases. The slow shortening was induced by tetanic electrical field stimulation, and changes in the cell length, volume and intracellular Cl- concentration were microscopically monitored using a chloride-sensitive fluorescent dye. The slow shortening was inhibited by a calmodulin inhibitor, W-7, and a calcium calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN-62. The inhibition by W-7 or KN-62, was abolished by the supplemented conductance of K+ with valinomycin. Among the protein phosphatase inhibitors tested, a type 1 and 2A protein phosphatase inhibitor, calyculin A, inhibited the slow shortening. The inhibition by calyculin A was abolished by the increased Cl- permeability, but neither by the increased K+ conductance with valinomycin nor by the increased Ca2+ conductance with A23187. A protein serine/threonine phosphatase activator, N-acetylsphingosine, inhibited the shortening, which was abolished by either valinomycin or a type 2A protein phosphatase inhibitor, okadaic acid, but not by calyculin A. These findings suggest the following signaling mechanisms in the slow shortening of outer hair cells; the K+ channel opening is facilitated through protein phosphorylation by CaMKII and suppressed via okadaic acid-sensitive dephosphorylation, and the Cl- channel opening depends on calyculin A-sensitive protein phosphatase activity.

Animals↗
PubMed1998

Breast masses: color Doppler, power Doppler, and spectral analysis findings.

PURPOSE: To determine the diagnostic efficacy of power Doppler sonography (PDS) with spectral analysis for breast diseases, we retrospectively compared PDS and color Doppler sonography (CDS) in patients with breast lesions. METHODS: One hundred thirty-eight women with palpable breast lesions were examined with PDS (65 women) and/or CDS (73 women). We calculated peak velocity, end-diastolic velocity, pulsatility index (PI), and resistance index (RI). RESULTS: On a 4-point subjective visual vascularity scale, PDS demonstrated higher vascularity than did CDS. Although smaller and more subtle vessels could be detected only with PDS, the PI and RI differed significantly between malignant and benign lesions when either PDS or CDS was used. However, logistic regression analysis showed that high PI and RI were associated with malignancy only when CDS was used. When PDS was used, PI was significantly higher in invasive ductal carcinomas with fibrous stroma and ill-defined margins (associated with a poor prognosis) than in invasive ductal carcinomas without fibrous stroma or with well-defined margins. CONCLUSIONS: Doppler spectral analysis of malignant breast lesions using PDS may contribute to the determination of prognosis.

Breast Neoplasms↗
PubMed1998

Radical surgery following neoadjuvant chemotherapy for patients with stage IIIB cervical cancer.

BACKGROUND: We conducted a phase II trial of radical surgery following neoadjuvant chemotherapy in patients with stage IIIB cervical cancer. METHODS: A total of 26 patients with stage IIIB cervical cancer were entered in this study. Patients were treated with a chemotherapeutic regimen consisting of intraarterial infusion of cisplatin and intravenous infusion of other anticancer agents, to a maximum of 3 courses. If the results of the evaluation indicated that surgery was feasible, radical surgery, including complete removal of pelvic vessels, partial resection of adjacent organs, and pelvic and paraaortic lymphadenectomy, was performed. Patients whose tumors showed no response received radiotherapy. We evaluated operability, survival rate, toxicities, and complications. Additionally, we examined prognostic variables by multivariate analysis in the patients treated by radical surgery. RESULTS: Eighteen patients (69.2%) underwent radical surgery. The remaining eight patients received radiation therapy. The 3-year disease-free survival rate was 72.2% in patients who received surgery and 25.0% in those who received radiotherapy. Multivariate analysis did not show any independent prognostic factors in the patients who underwent surgery. CONCLUSION: Radical surgery following neoadjuvant chemotherapy may be feasible in two thirds of patients with stage IIIB cervical cancer; therefore, phase III trials can be recommended.

Adult↗
PubMed1998

Does potassium ion concentration affect lung preservation?

To evaluate the influence of potassium ion concentration in an organ preservation solution on lung preservation, four types of solutions were produced. These preservation solutions consisted of sodium and potassium ions on the cation and phosphate ions on the anion with glucose. Contents of solutions were: (1) 155 mmol/l Na+, 0 mmol/l K+; (2) 150 mmol/l Na+, 5 mmol/l K+; (3) 20 mmol/l Na+, 135 mmol/l K+; and (4) 0 mmol/l Na+, 155 mmol/l K+. All four solutions possessed the same osmolarity, the same pH in the same temperature, and the same buffer action. Lungs were preserved at 7 degrees C in these solutions for 24 h and evaluated in a rat lung perfusion system with perfluorochemical emulsion. Pressure-limited perfusions with pressure-limited ventilation were carried out for 20 min before and after preservation. Thereafter, the recovery ratios of pulmonary arterial flow (Q), tidal volume (VT), oxygen tension of the pulmonary venous effluent (PPVO2), and wet-to-dry ratios were compared. The recovery ratios of Q were better in low, but not zero, potassium solutions, whereas wet-to-dry ratios were kept lower in high potassium solutions. No difference in pulmonary compliance or gas exchange was observed against a great change in potassium ion concentration. Therefore, the potassium ion concentration did not play a major role in lung preservation.

Animals↗