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O Inoue

Publications and source records attributed to O Inoue.

At least 19 recordsLinked to original sources

Phase II trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas.

We conducted a phase II trial to evaluate the efficacy and toxicity of radiotherapy immediately after hyperbaric oxygenation (HBO) with chemotherapy in adults with high-grade gliomas. Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO with the period of time from completion of decompression to irradiation being less than 15 min. Chemotherapy consisted of procarbazine, nimustine (ACNU) and vincristine and was administered during and after radiotherapy. A total of 41 patients (31 patients with glioblastoma and 10 patients with grade 3 gliomas) were enrolled. All 41 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. Of 30 assessable patients, 17 (57%) had an objective response including four CR and 13 PR. The median time to progression and the median survival time in glioblastoma patients were 12.3 months and 17.3 months, respectively. On univariate analysis, histologic grade (P=0.0001) and Karnofsky performance status (P=0.036) had a significant impact on survival, and on multivariate analysis, histologic grade alone was a significant prognostic factor for survival (P=0.001). Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10 and 7% of all patients, respectively, these were transient with no patients developing neutropenic fever or intracranial haemorrhage. No serious nonhaematological or late toxicities were seen. These results indicated that radiotherapy delivered immediately after HBO with chemotherapy was safe with virtually no late toxicity in patients with high-grade gliomas. Further studies are required to strictly evaluate the effectiveness of radiotherapy after HBO for these tumours.

Adult↗

Benzylmercapturic acid is superior to hippuric acid and o-cresol as a urinary marker of occupational exposure to toluene.

The present study was initiated to examine whether urinary benzylmercapturic acid (or N-acetyl-S-benzyl cysteine, BMA), a mercapturate metabolite of toluene, increases in relation to the intensity of toluene exposure, and whether this metabolite is a better marker of occupational exposure to toluene than two traditional markers, hippuric acid and o-cresol. Accordingly, end-of-shift urine samples were collected from 122 printers and 30 office clerks (all men) in the second half of a working week. Solvent (toluene) exposure of the day (8 h) was monitored by means of diffusive sampling. Quantitative relation with toluene showed that BMA had a greater correlation coefficient with toluene (r = 0.7) than hippuric acid (r = 0.6) or o-cresol (r = 0.6). The levels in the urine of the non-exposed control subjects were below the detection limit of 0.2 microg/l for BMA, whereas it was at substantial levels for hippuric acid and o-cresol (239 mg/l and 32 microg/l as a geometric mean, respectively). Thus, BMA, hippuric acid and o-cresol could separate the exposed from the non-exposed when toluene was at < 1, 50 and 3 ppm, respectively. Overall, therefore, it appeared reasonable to conclude that BMA is superior to hippuric acid and o-cresol as a marker of occupational exposure to toluene.

Acetylcysteine↗

Effect of rolipram on muscarinic acetylcholine receptor binding in the intact mouse brain.

The effect of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)) and elevating cyclic AMP (cAMP), on in vivo and in vitro (3)H-N-methylpiperidyl benzilate ((3)H-NMPB) binding to muscarinic acetylcholine receptors in the mouse brain was examined. Rolipram significantly decreased in vivo (3)H-NMPB binding in the cerebral cortex, hippocampus and striatum, whereas in vitro (3)H-NMPB binding in these regions was not altered. Saturation experiments on in vivo binding in conjunction with the kinetic analysis revealed that the apparent association rate constant (k(on)) of (3)H-NMPB binding in vivo was significantly decreased by rolipram. A similar decrease in the apparent association rate constant (k(on)) by rolipram was reported for dopamine D(1) and D(2) receptor binding in vivo. These results indicate that rolipram plays an important role in the global modulation of apparent rates of ligand-receptor interactions in the intact brain.

Animals↗

Effects of rolipram on in vivo dopamine receptor binding.

In order to clarify whether changes in brain concentrations of the second messenger cyclic AMP (cAMP) affect in vivo receptor binding in the brain, the effects of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)), on dopamine receptor binding in the mouse brain were studied. Rolipram significantly decreased in vivo (3)H-SCH 23390 (dopamine D(1) selective radioligand) binding in the mouse striatum in a dose-dependent manner. In vivo saturation experiments together with the kinetic analysis of (3)H-SCH 23390 binding revealed that the apparent association rate constant (k(on)) for (3)H-SCH 23390 binding rather than the maximum number of binding sites available (B(max)) was decreased by rolipram. (3)H-N-methylspiperone (NMSP, dopamine D(2) selective radioligand) binding in the mouse striatum was also decreased by rolipram whereas no significant changes in (3)H-raclopride (dopamine D(2) selective radioligand) binding were observed. As (3)H-raclopride binding has been reported to be much more sensitive than (3)H-NMSP binding to competition by endogenous dopamine, the decreases in (3)H-SCH 23390 and (3)H-NMSP binding cannot be attributed to competitive inhibition by endogenous dopamine. These results indicate that changes in second messenger cAMP concentrations may affect the apparent bimolecular association rate constant (k(on)) of dopamine receptor binding in intact brain. This may be mediated by changes in the receptor micro-environment and altered actual free ligand concentration surrounding the receptors.

3',5'-Cyclic-AMP Phosphodiesterases↗

The role of the cAMP-PKA system in the short-term regulation of striatal [(14)C]-2-deoxyglucose uptake in freely moving rats.

The cyclic adenosine monophosphate (cAMP)-protein kinase (PK) A system has been shown to have stimulatory effects on glucose utilization in various tissues in vitro. However, little is known about the influence of cAMP on glucose utilization in vivo. In the present study, we examined how cAMP-related compounds affected [(14)C]-2-deoxyglucose (DG) uptake in the striatum of freely moving rats. An intrastriatal injection of dibutyryl-cyclic adenosine monophosphate (db-cAMP), although increasing local cerebral blood flow, was found to decrease the uptake of [(14)C]-2-DG in the striatum. This decrease of [(14)C]-2-DG uptake in the striatum was completely blocked by pretreatment with Rp-adenosine-3',5'-cyclic monophosphorothioate triethylamine (Rp-cAMPS). Moreover, intrastriatal infusion of Rp-cAMPS alone produced a striking increase of [(14)C]-2-DG uptake in the striatum. These results strongly suggest that transient activation of the cAMP-PKA system can depress the glucose phosphorylation process of the rat brain in vivo.

Animals↗

Different sensitivities to competitive inhibition of benzodiazepine receptor binding of 11C-iomazenil and 11C-flumazenil in rhesus monkey brain.

The in vivo binding kinetics of 11C-iomazenil were compared with those of 11C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either 11C-iomazenil or 11C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 microg/kg). The regional distribution of 11C-iomazenil in the brain was similar to that of 11C-flumazenil, but the sensitivity of 11C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of 11C-flumazenil binding. A significant reduction in 11C-flumazenil binding in the cerebral cortex was observed with 20 microg/kg of flumazenil, whereas a relatively smaller inhibition of 11C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that 11C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain.

Animals↗

Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography.

Using positron emission tomography (PET) and [11C]N-methylspiperone (NMSP), we examined 5-HT2 receptors in the cortex of schizophrenic patients in whom we previously observed decreased prefrontal D1 receptor binding. The subjects were 10 neuroleptic-naive schizophrenic patients, 7 schizophrenic patients who were drug-free but had previously been treated with neuroleptics, and 12 normal controls. A non-significant trend towards decreased prefrontal [11C]NMSP binding was observed in the neuroleptic-treated patients, suggesting a possible effect of previous neuroleptic treatment on the alteration in cortical 5-HT2 function. However, the neuroleptic-naive patients showed no noticeable difference in cortical [11C]NMSP binding compared to controls. Our results do not rule out the role of 5-HT2 function as a crucial site of therapeutic activity of schizophrenia, but they do suggest that cortical 5-HT2 receptors might not be primarily involved in the pathophysiology of schizophrenia.

Adult↗

Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection.

BACKGROUND/AIM: Time-dependent intrahepatic recurrence of hepatocellular carcinoma is frequent after different treatment modalities, including percutaneous ethanol injection. We attempted to prospectively analyze the possible risk factors for early intrahepatic recurrence of hepatocellular carcinoma after percutaneous ethanol injection. METHODS: Sixty-five patients with 65 solitary hepatocellular carcinoma nodules < or =6 cm in diameter underwent initial treatment with percutaneous ethanol injection and were examined to ascertain the factors related to recurrence, local and distant, within the liver. A number of clinical and tumor parameters were analyzed. RESULTS: Cumulative overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 15.6% and 45.1%, respectively, irrespective of clinical and tumor parameters. Overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 40% and 67.5%, for tumor > or =3 cm and 7.5% and 37.5%, for tumor <3 cm. Cumulative local recurrence rates at 12 and 24 months were 26.3% and 43.5%, respectively, for tumor > or =3 cm and 11.7% and 18.2%, respectively, for tumor <3 cm. The log-rank test indicated that a tumor size of > or =3 cm and the presence of capsule for a tumor of <3 cm in diameter were significant risk factors for intrahepatic recurrence. A pretreatment serum PIVKA-II level of > or =0.02 AU/ml was the only clinical parameter associated with overall recurrence (p=0.0041) and distant intrahepatic recurrence (p=0.0307). Distant intrahepatic recurrence rates 12 and 24 months after percutaneous ethanol injection were 22.5% and 31.4%, respectively, for PIVKA-II levels of > or =0.02 AU/ml and 8% and 17.8%, for PIVKA-II of <0.02 AU/ml. Cox's proportional hazard model identified that tumor size, tumor capsule and baseline serum PIVKA-II levels were independently related to intrahepatic recurrence. CONCLUSIONS: These data demonstrate that tumor size and peritumoral capsule were associated with overall and local recurrence of hepatocellular carcinoma. Moreover, pretreatment serum levels of PIVKA-II can indicate the risk of early intrahepatic recurrence and may assist in patient selection and appropriate therapy.

Adult↗

Detection of HBV RNA in peripheral blood mononuclear cells in patients with and without HBsAg by reverse transcription polymerase chain reaction.

We examined RNA of hepatitis B virus (HBV) in peripheral blood mononuclear cells (PBMCs) by the reverse transcription polymerase chain reaction (RT PCR) in 61 patients associated with HBV infection, in order to analyze the relationship between the transcriptional activity of HBV in PBMCs and the clinical characteristics. The presence of HBV RNA in PBMCs was detected in 19/51(37.1%) patients with HBsAg positive and in 1/10 (10.0%) patient with HBsAg negative patients. Six healthy controls were all negative. The frequency of HBV RNA positivity was detected in patients with high ALT level (P<0.05), serum HBeAg positivity (P<0.01) and serum HBV DNA level>/=0.7 Meq/ml (P<0.05). Moreover, HBV RNA in PBMCs was detected in one patient followed up for 2 years after HBsAg disappearance in serum, who had not HBV DNA but anti-HBc IgG, in serum. These results suggested that the transcription of HBV in PBMCs, was frequently detected in the patients with higher replication of the virus, but HBV RNA in PBMCs might be detected in a few patients who had no evidence of HBV replication serologically.

Journal Article↗

Proposed abdominal sonographic staging to predict severity of liver diseases: analysis with peritoneoscopy and histology.

Abdominal sonography is a routinely used noninvasive modality for screening and treatment of liver diseases. We attempted to establish a morphological sonographic staging to predict the severity of liver diseases with their consequent analysis with morphological staging of peritoneoscopy and histology. In all, 136 patients were enrolled for the final confirmation of disease state by peritoneoscopy and histology preceded by abdominal sonography. All patients were categorized from stage 0 to stage 5, depending on a proposed criterion of sonographic features based on surface pattern of liver and the appearance of internal echogenic bands relating to the irregularity of the liver texture. A digitized computer quantitation of histogram-based standard deviation (SD) values from different stages of sonographic images was analyzed, and their values were justified by correlation with the definite appearance of an internal echogenic band. The association of different sonographic stages with disease progression was also demonstrated by their relation with peritoneoscopy and histology. In all patients, the different sonographic staging results were significantly correlated with hepatic surface features of peritoneoscopic staging (r = 0.939, P < 0.0001) graded from stage 0 to stage 5 and were also correlated with biopsy-proven staging of fibrosis (r = 0.739, P < 0.0001). The greater SD values of histogram-based echo levels, as analyzed from digitized sonographic images of 90 patients, were associated with the appearance of internal echogenic bands (P < 0.0001). Furthermore, the corresponding SDS were significantly correlated with the qualitative staging of sonographic features (r = 0.781, P < 0.0001), peritoneoscopy (r = 0.786, P < 0.0001) and histology (r = 0.779, P < 0.0001). We concluded that our proposed sonographic staging is well correlated with peritoneoscopic and histological staging of liver diseases, with only a small discrepancy, and can be used clinically to demonstrate the ongoing severity of liver diseases.

Abdomen↗

Short- and long-term survival and prevalence of postoperative ileus after small intestinal surgery in the horse.

The records of 74 horses that recovered from anaesthesia after surgery for a small intestinal lesion from 1994 to 1999 were reviewed. Sixty-three horses (85%) had a strangulating lesion and 43 of these (68%) had a resection and anastomosis. Four of 11 horses (36%) without a strangulating lesion had a resection and anastomosis. Sixty-three horses (85%) survived to discharge, with a survival rate of 53/63 in horses with a strangulating lesion (84%) and 10/11 (91%) in others. For all lesions, short-term survival for all end-to-end anastomoses (91%; 21/23) and for no resection (92%; 23/25) were superior (P < 0.05) to survival for jejunocaecal anastomosis (76%; 19/25). Fourteen horses (19%) had a repeat abdominal surgery during hospitalisation; 9 of these (64%) survived short-term. Postoperative ileus developed in 7/70 horses (10%) after surgery for a problem other than proximal enteritis, and all had a strangulating lesion. Postoperative ileus (POI) was more likely after a jejunocaecostomy than after other procedures, and did not develop after a jejunojejunostomy. Survival > 7 months was 52/69 (75%) and for > 12 months was 39/57 (68%). The estimated prevalence of adhesions was 13%. Short-term survival was poorest in horses that had a jejunocaecostomy, but long-term survival was less affected by the anastomosis used. The sharpest decline in survival was during the first postoperative week and postoperative mortality then declined over time after surgery. A postoperative protocol that allowed early postoperative feeding was well tolerated. The results confirm that the overall prognosis after small intestinal surgery in horses is improved over earlier findings.

Anastomosis, Surgical↗

Urinary phenylmercapturic acid as a marker of occupational exposure to benzene.

A hand-saving HPLC method to measure urinary phenylmercapturic acid (PMA) was developed which allows about 35 PMA determinations per day. The method involves conversion of pre-PMA to PMA by the addition of sulfuric acid to a urine sample, extraction into an ether-methanol mixture followed by condensation under a nitrogen stream. The condensate was introduced to a ODS-3 column in a HPLC system, and PMA in the column was eluted into a mobile phase of acetonitrile: methanol: perchloric acid: water. The elution of PMA was monitored at 205 nm. One determination will be completed in 40 min. The method was applied to analysis of end-of-shift urine samples from 152 workers exposed up to 210 ppm benzene, 66 workers exposed to a mixture of benzene (up to 116 ppm) and toluene + xylenes (up to 118 ppm), and 131 non-exposed controls of both sexes. A linear regression was established between time-weighted average intensity of exposure to benzene and urinary PMA. From the regression, it was calculated that urinary PMA level will be about 6.4 mg/l after 8-hour exposure to benzene at 100 ppm, and that PMA in urine accounted for about 0.1% of benzene absorbed. No effects of sex, age, and smoking habit of individuals were detected, and the effect of co-exposure to toluene + xylenes at the levels comparable to that of benzene was essentially nil, which indicates an advantage of PMA as a benzene exposure marker over monoto tri-phenolic metabolites or t,t-muconic acid.

Acetylcysteine↗

[Characteristics of Papaver somniferum L. cv. ikkanshu cultivated in Izu].

The seeds of Papaver somniferum L. cv. Ikkanshu were sown in November (Autumn sowing: AS) and March (Spring sowing: SS) in a field at Izu Experimental Station for Medicinal Plants of National Institute of Health Sciencs, and both AS and SS plants were cultivated to investigate their growth, opium yield and alkaloid content in the opium. Growing periods from the sowing to the opium harvest were approximately six months for AS plants and three months for SS plants. Sizes of plants and capsules in AS were bigger than those in SS, reflecting their growth period. Opium yields per an are in AS and SS were 212.09 g and 142.03 g, respectively. The opium was able to be collected four times in the AS plants though the SS plants ceased to exude opium after the second incision. Therefore higher yield of opium in AS plants seems to be attributed to an amount of opium in the third and fourth incision. Average morphine content in the total opium was 15.61% in AS plants and 15.04% in SS plants, and the estimated amounts of morphine per an are in AS and SS plants were 33.16 g and 21.38 g, respectively.

Government Agencies↗

Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy.

BACKGROUND: Previous studies on the effect of interferon therapy on the incidence of hepatocellular carcinoma have not sufficiently assessed degree of liver fibrosis, a major risk factor for hepatocellular carcinoma. OBJECTIVE: To evaluate the effect of interferon therapy on incidence of hepatocellular carcinoma, adjusting for risk factors, including the degree of liver fibrosis. DESIGN: Retrospective cohort study. SETTING: Seven university hospitals and one regional core hospital in Japan. PATIENTS: 2890 patients with chronic hepatitis C who had undergone liver biopsy since 1986. Of these patients, 2400 received interferon and 490 were untreated. MEASUREMENTS: The degree of liver fibrosis was assessed from stage F0 (no fibrosis) to stage F4 (cirrhosis). Response to interferon was determined virologically and biochemically. Screening for development of hepatocellular carcinoma was performed periodically during an average follow-up of 4.3 years. Effect of interferon therapy on the risk for hepatocellular carcinoma was analyzed by using Cox proportional hazards regression. RESULTS: Hepatocellular carcinoma developed in 89 interferon-treated patients and in 59 untreated patients. Among untreated patients, the annual incidence of hepatocellular carcinoma increased with the degree of liver fibrosis, from 0.5% among patients with stage F0 or F1 fibrosis to 7.9% among patients with stage F4 fibrosis. The cumulative incidence in treated and untreated patients differed significantly for patients with stage F2 fibrosis (P = 0.0128) and for those with stage F3 fibrosis (P = 0.0011). In multivariate analysis, interferon therapy was associated with a reduced risk for hepatocellular carcinoma (adjusted risk ratio, 0.516 [95% CI, 0.358 to 0.742]; P < 0.001), especially among patients with sustained virologic response (risk ratio, 0.197 [CI, 0.099 to 0.392]), among those with persistently normal serum alanine aminotransferase levels (risk ratio, 0.197 [CI, 0.104 to 0.375]), and among those with alanine aminotransferase levels less than two times the upper limit of normal (risk ratio, 0.358 [CI, 0.206 to 0.622]). CONCLUSIONS: Interferon therapy significantly reducesthe risk for hepatocellular carcinoma, especially among virologic or biochemical responders.

Alanine Transaminase↗

Enhancement of 3H-N-methylspiperone binding but not 3H-raclopride binding in mouse striatum by MK-801: evidence that factors other than competition by endogenous dopamine are responsible for changes in D2 receptor binding in vivo. Short communication.

The effect of acute pretreatment with MK-801 on the binding in vivo of both 3H-N-methylspiperone (NMSP) and 3H-raclopride (RAC) were compared in mice. In the striatum, MK-801 significantly increase 3H-NMSP binding, whereas no significant alterations in 3H-RAC binding were seen. In contrast, binding in the cerebral cortex of both radiolabeled ligands was not changed by MK-801. Kinetic analysis revealed that the increase in 3H-NMSP binding induced by MK-801 was due to an increase in the rate constant k3(k3 = kon.Bmax). In vivo saturation experiments showed that Bmax for 3H-NMSP binding was relatively unchanged and an increase in the apparent association rate constant (kon) was the main reason for an increase in the k3 for 3H-NMSP binding. As 3H-RAC binding is known to be much more sensitive to competitive inhibition than is 3H-NMSP binding, these results strongly suggest that factors other than competition by endogenous dopamine may contribute to changes in receptor binding in vivo caused by NMDA-antagonism.

Animals↗

Discrepancy of benzodiazepine receptor occupancy between 3H-flumazenil and 125I-iomazenil in intact mouse brain.

The in vivo benzodiazepine (BZ) receptor occupancy in mouse brain was measured by employing 3H-flumazenil (FMZ) in comparison with 125I-iomazenil (IMZ), in order to obtain fundamental data for PET and SPECT studies, respectively. Mice were pretreated with various doses of flunitrazepam (FNP) 40 min prior to the tracer injection. At 20 min after the tracer injection, mice were killed by decapitation and receptor occupancy in cerebral cortex, hippocampus, cerebellum and pons-medulla were determined by the modified method reported by Goeders and Kuhar (1985). In all regions studied, BZ receptor occupancy by FNP measured with 3H-FMZ was significantly higher than that of 125I-IMZ. For instance, 0.1 mg/kg of FNP inhibited almost 50% of the specific binding of 3H-FMZ, on the other hand almost no inhibition of 125I-IMZ with the same dose of FNP was seen. This type of discrepancy was also observed in other types of benzodiazepine agonists, nimetazepam and triazolam, or inverse agonist ethyl-beta-carboline-3-carboxylate (CCE). It is of interest that in in vitro binding study using brain homogenate, almost the same competitive inhibition curve was observed between these two radioligands, which strongly suggested that discrepancy of receptor occupancy is likely observed in intact brain. The mechanism for such discrepancy is unknown, although the different kinetics properties of these two radioligand seems to be an important factor.

Animals↗

Evaluation of in vivo binding properties of 3H-NMPB and 3H-QNB in mouse brain.

UNLABELLED: Apparent muscarinic acetylcholine (mAch) receptor occupancy in mouse cerebral cortex, hippocampus, and striatum by scopolamine, an antagonist, and biperiden, a relatively selective M1 antagonist, was estimated with competitive binding studies using two different radioligands: 3H-N-methyl piperidyl benzilate (3H-NMPB) and 3H-quinuclidinyl benzilate (3H-QNB). Both radioligands labeled mAch receptors in these brain regions, and the relative regional distributions of the specific binding of 3H-NMPB in vivo paralleled the distribution of mAch receptors. 3H-NMPB binding in vivo was much more sensitive to direct competitive inhibition by scopolamine than was 3H-QNB. A similar discrepancy in sensitivity to competitors between 3H-NMPB and 3H-QNB was also observed when biperiden was used as a competitor, indicating that binding to different subtypes of the mAch receptor could not account for the observed differences in sensitivity to competition. An in vivo saturation study suggested that the apparent association rate constant (k on) of 3H-QNB binding might be changed by ligand concentration. The heterogeneity of the free ligand concentration in intact brain was assessed in relation to the ligand concentration dependency of the apparent association rate constant (k on) of 3H-QNB binding. This finding, together with the more favorable accumulation of 3H-NMPB in cerebral cortex, hippocampus, and striatum, leads us to conclude that 3H-NMPB, or its positron emitting counterpart, should be the more favorable radiotracer for the estimation of mAch receptor occupancy by cholinergic drugs in the brain. KEYWORDS: mAch receptor, QNB, NMPB, in vivo, mouse.

Animals↗