Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 289 records · Page 16Linked to original sources

PubMed1998

Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice.

The physiological role of the prostaglandin E2 receptor EP4 subtype was investigated by generation of EP4-deficient-mice by gene targeting. Loss of the EP4 receptor was not lethal in utero, but most EP4 (-/-) neonates became pale and lethargic approximately 24 h after birth and died within 72 h. Less than 5% of the EP4 (-/-) mice survived and grew normally more than a year. Histological examination revealed that the ductus arteriosus in dead neonates remained open, while it was partially closed in the survivors. In situ hybridization study showed that EP4 mRNA was strongly expressed in the ductus. These results suggest that neonatal death is at least partly due to patent ductus arteriosus and that the EP4 receptor plays a role in regulation of the patency of this vessel. They also indicate that normal function of the EP4 receptor is essential in neonatal adaptation of the circulatory system.

Animals↗

PubMed1998

A compact vacuum-ultraviolet beamline for synchrotron radiation photoelectron spectroscopy combined with an ion-scattering spectrometer, SORIS.

Apparatus for high-resolution synchrotron radiation photoelectron spectroscopy combined with high-resolution medium-energy ion scattering, named 'SORIS', has been developed for simultaneous investigations of electronic states and atomic structures on surfaces. For this purpose, a compact vacuum-ultraviolet beamline of photon energy from 5 to 700 eV has been designed for the small storage ring 'Aurora' installed at Ritsumeikan University. Owing to the small electron-beam size in the storage ring, an energy resolution E/dE of >5000 can be obtained.

Journal Article↗

PubMed1998

Association between expression of glutathione-associated enzymes and response to platinum-based chemotherapy in head and neck cancer.

We examined the correlation between response to platinum-based chemotherapy and expression of glutathione S-transferase (GST), gamma-GGT (both by immunohistochemistry) and gamma-GCS (by in situ hybridization) in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (CR, PR) for patients with low GST scores was 88% (21 of 24), while among the patients with high GST scores, the overall response rate was 19% (6 of 32, P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST score was 70% (7 of 10), while among the patients with high GST scores, the overall response rate was 8.7% (2 of 23), P < 0.001). In contrast, both gamma-GCS and gamma-GGT showed a range of expression in these samples, but there was no significant correlation with treatment response. We conclude that GST expression correlates well with response to platinum based chemotherapy in head and neck cancer.

Aged↗

PubMed1998

Origin and mechanism of formation of 45,X/47,XX,+21 mosaicism in a fetus.

Chromosome analysis of amniotic fluid cells from a 17-week-old fetus with a nuchal cystic hygroma showed a 45,X/47,XX,+21 karyotype. Analyses of cord blood lymphocytes, skin fibroblasts, amniotic membrane, and chorionic villi demonstrated both cell lines in various proportions. We studied the origin and mechanism of formation of the double mosaic aneuploid using Q-banded chromosomal heteromorphisms, and one RFLP, two VNTRs, one tetranucleotide repeat, 28 CA repeat markers, mapped to every member of chromosomes. The heteromorphic markers examined showed no discordant patterns in parent-to-child transmission or between the two cell lines except for those in chromosomes 21 and X. Fetal DNA was extracted from its established monoclonal fibroblast cell lines with 45,X or 47,XX,+21 karyotypes. Genotyping with the DNA markers showed that each cell line was identical at every locus, except for chromosome 21 or X loci, indicating that the fetus was not a chimera but a mosaic. The 21-trisomic cells had one paternal allele and two maternal heterozygous alleles at the D21S270 locus, and the 45,X (21-disomic) cells had two biparental alleles. Alleles at two X chromosomal loci, DXS991 and DXS8057, were biparental in the 47,XX,+21 cells, whereas only the paternal allele was retained in the 45,X cells. Based on these findings, we concluded that the fetus started as a 47,XX,+21 zygote that had resulted from nondisjunction at the maternal first meiotic division and that one each of the maternally derived chromosomes 21 and X was lost during an early mitotic division, leading to the mosaicism.

Alleles↗

PubMed1998

Acute and chronic administration of clozapine produces greater proconvulsant actions than haloperidol on focal hippocampal seizures in freely moving rats.

In this study, we assessed the effects of the acute (a single injection) and repeated (once daily injections for 21 days) administration of the atypical antipsychotic drug clozapine (1.5, 5, or 15 mg/kg i.p.) and the typical antipsychotic drug haloperidol (0.15, 0.5, and 1.5 mg/kg, i.p.) on hippocampal partial seizures generated by low-frequency electrical stimulation in male Wistar rats. The seizure threshold and severity were determined by measuring the pulse number threshold (PNT) and the primary afterdischarge duration (ADD), respectively. A single injection of either 5 or 15 mg/kg of clozapine significantly decreased the PNT and significantly increased the primary ADD, indicating a proconvulsant action. The repeated administration of clozapine (1.5, 5, or 15 mg/kg, i.p.) produced dose-dependent, proconvulsant effects by significantly decreasing the PNT and by significantly increasing the primary ADD. In contrast to clozapine, the acute administration of haloperidol did not significantly alter the PNT or the primary ADD. The repeated administration of haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike clozapine, significantly decreased the primary ADD, but did not alter the PNT. Overall, clozapine produces a greater proconvulsant action than haloperidol in an animal model of hippocampal seizures.

Animals↗

PubMed1998

Enhancement of in vivo binding of [123I]beta-CIT by MK-801 in rat brain.

The effects of MK-801, a noncompetitive NMDA receptor antagonist, on in vivo and in vitro binding of radioactive iodine ([123I] or [125I]) labeled beta-CIT [RTI-55, 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester] were investigated in rat brain. In the in vitro binding study, 10 pM of [125I]beta-CIT was incubated with either 0.03 microM or 3 microM of MK-801 at 24 degrees C for 60 min. In vitro, no alterations in [125I]beta-CIT binding in any region of rat brain slices were detected after addition of MK-801. In the in vivo binding study, [123I]beta-CIT was intravenously injected into rats 30 min after intraperitoneal injection of 0.03-1 mg/kg of MK-801. The in vivo [123I]beta-CIT binding in the striatum, frontal cortex, occipital cortex, hypothalamus, and thalamus was significantly increased by pretreatment with 1 mg/kg of MK-801. Kinetic analysis using the cerebellum as a reference region revealed that the increases in in vivo [123I]beta-CIT binding induced by MK-801 were mainly due to increases in both input rate constant k3 and output rate constant k4. The results of this study indicate that the glutamatergic system, including NMDA receptor, plays an important role in regulating neurotransmission in the dopaminergic or serotonergic systems in intact brain.

Animals↗

PubMed1998

Effects of hepatocyte growth factor, transforming growth factor-beta1 and epidermal growth factor on bovine corneal epithelial cells under epithelial-keratocyte interaction in reconstruction culture.

In the cornea, corneal epithelial cells are in close contact with keratocytes: the epithelial cells organize thickened lamellar structure on a layer of keratocytes embedded in extracellular matrix (ECM). Thus, growth factors are expected to critically regulate corneal component cells under epithelial-keratocyte interaction. The purpose of this study is to clarify effects of hepatocyte growth factor (HGF), transforming growth factor-beta1 (TGF-beta1) or epidermal growth factor (EGF) on corneal epithelial cells under epithelial-keratocyte interaction. We examined proliferation and differentiation of the epithelial cells in a simple corneal reconstruction culture composed of an epithelial cell layer on the keratocyte-containing stromal layer, using three-dimensional collagen gel matrix culture. We observed the morphological change by phase contrast microscopy, and conducted histological and immunohistochemical examinations. The epithelial proliferation was examined by nuclear bromodeoxy-uridine (BrdU) uptake. In the reconstructed cornea under epithelial-keratocyte interaction, EGF-, TGF-beta1- and HGF-treated cells formed a thickened epithelial layer consisting of 5-6, 5-6 and 3-4 cells, respectively. In fact, both EGF and TGF-beta1 induced significantly higher intakes of nuclear BrdU of the epithelial cells than HGF. In lamellar differentiation of the epithelial cells, TGF-beta1- or HGF-treated cells formed a triple lamellar structure specific for the in vivo corneal epithelium: basal, middle and superficial layers are composed of cuboidal basal-like cells, spindle wing-like cells and flat superficial-like cells, respectively. TGF-beta1-treated cells formed a more markedly thickened epithelial layer than HGF-treated cells. In contrast, EGF formed a single lamellar structure consisting of cuboidal cells. These results suggest that those growth factors regulate proliferation and/or lamellar differentiation of corneal epithelial cells under epithelial-keratocyte interaction. The most interesting result was that TGF-beta1 promotes proliferation and lamellar differentiation of corneal epithelial cells through keratocyte-mediated stimulation.

Animals↗

PubMed1998

NMDA receptors in the inferior colliculus are critically involved in audiogenic seizures in the adult rats with neonatal hypothyroidism.

The effects of N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists were compared on audiogenic seizures in the rats neonatally exposed to propylthiouracil (PTU). The rats treated with 0.02% PTU through mother's milk during days 0-19 after delivery showed a high incidence of audiogenic seizures consisting of running fit (RF) followed by generalized tonic-clonic seizure (GTCS) after matured. The systemic administration with MK-801, a NMDA receptor antagonist dose-dependently inhibited both RF and GTCS. NBQX (6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione), a non-NMDA receptor antagonist, when systemically administered, failed to block audiogenic seizures. Audiogenic seizures caused a marked induction of c-fos messenger RNA (mRNA) in septal nucleus, bed nucleus of stria terminalis, amygdaloid nuclei, peripeduncular nucleus, and inferior colliculus, which was almost completely blocked by the pretreatment with MK-801. Bilateral microinjection of MK-801 into the inferior colliculus showed a tendency for inhibiting GTCS, but not RF, whereas CPP (3-(R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid), a competitive NMDA receptor antagonist produced a significant inhibition against both RF and GTCS. These NMDA receptor antagonists administered into cisterna ambience, the floor of which is composed of inferior colliculus and neighboring structures, have shown potent blocking effects on both RF and GTCS. The present results suggest that NMDA receptors in the inferior colliculus, presumably in the subnucleus of external cortex may play the critical role in the initiation of audiogenic seizures in PTU-treated rats.

Acoustic Stimulation↗

PubMed1998

Determination of a normal level of serum CA125 in postmenopausal women as a tool for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

In an attempt to determine a normal level of CA125 in postmenopausal women, CA125 levels of normal postmenopausal women (n = 36, 58.2 +/- 8.1 years) and postmenopausal women undergoing hormone replacement therapy (HRT) (n = 111, 56.8 +/- 6.1 years) were studied. A mean CA125 concentration of 10.0 +/- 3.8 U/ml was found in postmenopausal women without HRT and was significantly lower than that of postmenopausal women undergoing HRT (12.8 +/- 3.8 U/ml), indicating that the cutoff level of CA125 in postmenopausal women or women without reproductive organs should be estimated at a level lower than that conventionally accepted. A receiver operating characteristic (ROC) curve for a preoperative evaluation of myometrial invasion was analyzed in postmenopausal women with endometrial cancer (n = 110). A novel cutoff level of 20 U/ml of CA125 could detect myometrial invasion to more than one-half of the myometrium with sensitivity of 69.0%, specificity of 74.1%, positive predictive value of 58.8%, and negative predictive value of 81.6%. In addition, the distribution of CA125 levels was analyzed in patients who had undergone an operation for endometrial cancer more than 2 years earlier and as yet had no clinical evidence of recurrence of the disease. Ninety-six point two percent of 619 measurement values were lower than 20 U/ml. These results suggest that the novel CA125 level of 20 U/ml is clinically useful for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

Aged↗

PubMed1998

Alteration of intracellular Na+ during ischemia in diabetic rat hearts: the role of reduced activity in Na+/H+ exchange against stunning.

To elucidate the contribution of reduced activity of Na+/H+ exchange in streptozotocin-induced diabetic hearts against stunning, intracellular Na+ concentration ([Na+]i) was measured in isolated rat hearts using 23Na-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37 degreesC was significantly better in diabetic ones (102.9+/-2.0% of pre-ischemic level, mean+/-s.e., n=6; P<0.05), and non-diabetic ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 mu mol/l; 93.8+/-2.3%, n=5; *P<0.05) than non-treated, non-diabetic hearts (75.1+/-2.5%, n=8). When diabetic hearts were pre-treated with EIPA, the recovery (101.2+/-2.6%, n=5) was identical to that of non-treated, diabetic hearts. [Na+]i in non-diabetic hearts increased to 329.1+/-8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+]i in diabetic hearts significantly suppressed to 199.8+/-10.3% (P<0.001). EIPA attenuated the increase of [Na+]i during ischemia to 189.1+/-9.0% in non-diabetic hearts ( P<0.001) and to 155.3+/-4.6% in diabetic hearts (P<0.05). Thus, the EIPA-dependent Na+ accumulation during ischemia, i.e. Na+ influx probably mostly via Na+/H+ exchange was smaller in diabetic hearts by 69.7% compared with that in non-diabetic hearts. These results indicate that the cardiac protection against stunning in streptozotocin-induced diabetic hearts is mediated by the attenuation of Na+ accumulation during ischemia, which is caused by the reduced activity in Na+/H+ exchanger.

Adenosine Triphosphate↗

PubMed1998

Difference in the mechanisms for compensating ischemic acidosis in diabetic rat hearts.

To elucidate the difference in the mechanisms for alkalization during ischemic acidosis between diabetic and non-diabetic hearts, intracellular pH (pHi) was measured by phosphorus-31 magnetic resonance spectroscopy. Diabetes was induced by the injection of streptozotocin. The accumulation of proton ion (DeltaH+) during 15 min global ischemia at 37 degreesC was calculated from pH i. There were no significant differences in DeltaH+ between diabetic (DM: 0. 54+/-0.03 micromol/l,n=6; mean+/-s.e.m.) and non-DM hearts (0.57+/-0.04, n=6), when perfused with bicarbonate buffer. However, perfusion with HEPES buffer revealed a significant increase of DeltaH+ in DM (0.85+/-0.07, n=5) compared with non-DM (0.61+/-0.06, n=5P<0.05). On the contrary, the addition of a Na+/H+ exchange inhibitor (EIPA; 1 micromol/l) to bicarbonate buffer significantly increased DeltaH+ in non-DM (1.09+/-0.10, n=4) compared with DM (0.71+/-0.03, n=5P<0.01). Perfusion with HEPES buffer and EIPA equally increased DeltaH+ in both groups (DM 1.13+/-0.13, n=4; non-DM 1.15+/-0.14, n=4). Thus, the activity of Na+/H+ exchanger during ischemic acidosis, assessed as the increase of DeltaH+ induced by addition of EIPA to bicarbonate buffer, was higher in non-DM (0.52) than DM (0.17). In contrast, the contribution of bicarbonate-dependent systems evaluated by the deference of DeltaH+ between the bicarbonate buffer and the HEPES buffer was markedly bigger in DM (0.31) than non-DM (0.04). These results indicate that Na+/H+ exchange is a major mechanism to compensate ischemic acidosis in non-DM hearts, whereas bicarbonate-dependent systems compensate the depressed activity of Na+/H+ exchange in DM.

Acidosis↗

PubMed1998

Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy: assessment by F-18-FDG PET study.

In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75 +/- 0.34%, 0.65 +/- 0.25%, and 0.43 +/- 0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17 +/- 0.49%, 0.80 +/- 0.44% and 0.99 +/- 0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38 +/- 0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy.

Blood Glucose↗

PubMed1998

Prediction of functional recovery and prognosis in patients with acute myocardial infarction by 123I-BMIPP and 201Tl myocardial single photon emission computed tomography: a multicenter trial.

123I-BMIPP [15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid] was developed for metabolic imaging with SPECT. A multicenter collaborative study was conducted on a large patient series to determine whether 123I-BMIPP and 201Tl myocardial SPECT are of use in predicting the prognosis and ventricular function after acute myocardial infarction (AMI). Patients with uncomplicated first AMI underwent resting 123I-BMIPP and 201Tl myocardial SPECT in the subacute phase after the onset of AMI. Of these, 167 patients who had been followed up for an average of 22 months were retrospectively reviewed to predict serious cardiac events and recurrent ischemia. In addition, the association between changes in radionuclide parameters and recurrent ischemia was investigated in Subgroup A (58 patients) who had repeated SPECT in the chronic phase. Furthermore, prediction of the ejection fraction (EF) was investigated in Subgroup B (94 patients) and Subgroup C (76 patients) in whom left ventriculography was performed at the time of discharge and 90 days or more after the onset, respectively. The prognosis was generally favorable, with 4 cases of cardiac death (2%), 3 of heart failure (2%), 4 of nonfatal reMI (2%), and 25 of recurrent ischemia (15%). The results of Cox multivariate regression analysis revealed a high probability of serious cardiac events in patients who were elderly (p = 0.04), who had 90% or more residual stenosis of the infarct-related artery (p = 0.09), and who had a high BMIPP defect score (p = 0.17). There was a high probability of recurrent ischemia in elderly patients (p = 0.10) who had multi-vessel disease (p = 0.03), but no association was found with radionuclide parameters in the subacute phase. In Subgroup A, however, the probability of recurrent ischemia tended to be high in patients with a large mismatch scorebetween 123I-BMIPP and 201Tl in the subacute to chronic phase. An important observation was that the extent of BMIPP defect was more strongly correlated with EF at the time of discharge and 90 days or more after the onset than the extent of Tl defect (r = -0.60 vs. r = -0.47, and r = -0.53 vs. r = -0.43, respectively). In addition, multiple regression analysis showed that parameters related to the BMIPP defect were also better predictive factors of EF both at the time of discharge and 90 days or more after the onset. In conclusion, resting 123I-BMIPP and 201Tl myocardial SPECT performed in the subacute phase of AMI were shown to be useful in predicting prognosis and ventricular function for patient management.

Aged↗

PubMed1998

Glucose tolerance and myocardial F-18 fluorodeoxyglucose uptake in normal regions in coronary heart disease patients.

To elucidate the relation between glucose tolerance and myocardial uptake of F-18 fluorodeoxyglucose (FDG), FDG-PET with 75 g oral glucose loading was performed on 43 coronary artery disease patients (twice in 2 patients). The patients were divided into 4 groups based on the blood glucose level (BS) and the insulinogenic index (II): group 1, normal (n = 9); group 2, impaired glucose tolerance (IGT, n = 12); group 3, mild diabetes mellitus (DM) (II > 0.4, n = 12); and group 4, severe DM (II < or = 0.4, n = 12). Percent (%) dose uptake of FDG in the normal regions of the myocardium was not significantly different in groups 1, 2, and 3, but it was much lower in group 4 than in groups 1 and 2. In groups 2, 3, and 4, % dose uptake showed a definite negative correlation with BS 60 min after glucose loading (r = -0.450, p < 0.05), and a close positive correlation with II (r = 0.363, p < 0.05). These findings indicate that myocardial FDG uptake in normal regions is not greatly impaired in patients with IGT or mild DM. Myocardial viability can be assessed by oral glucose loading in patients with IGT and mild DM as well as in patients with normal glucose tolerance.

Aged↗

PubMed1998

Acetazolamide induced myocardial ischemia in patients with severe coronary artery disease.

UNLABELLED: Acetazolamide (ACZ)-augmented brain SPECT is commonly used for evaluating cerebral vascular reserve in patients with cerebrovascular disease. ACZ may cause myocardial ischemia in patients with coronary artery disease. To evaluate the risk of induction of myocardial ischemia with ACZ-augmented myocardial SPECT, we performed combined ACZ-augmented Tl-201 myocardial SPECT (ACZ-myo SPECT) with Tc-99m HMPAO brain SPECT in patients with severe coronary artery disease. METHODS: Nine patients underwent combined ACZ-myo SPECT with Tc-99m HMPAO brain SPECT. (1) For qualitative analysis, SPECT images were divided into 13 segments to calculate the total defect scores. (2) Six ROIs were placed on the slices in the myocardial SPECT short-axis images and the regional uptake ratio was obtained as the ratio of the mean counts in the myocardium to the maximal count in the slice. The total defect score and regional uptake ratio of ACZ-myo SPECT were compared with those of early and delayed dipyridamole Tl-201 myocardial SPECT (DP-Tl SPECT) images. RESULTS: (1) In the 21 coronary artery territories with coronary stenosis > or = 75%, the total defect score in ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 3.52 +/- 4.14*, 4.19 +/- 4.65* and 2.25 +/- 3.34, respectively (*: p < 0.05 vs. delayed DP-Tl SPECT images). (2) In 44 of 54 ROIs with coronary stenosis > or = 75%, the regional uptake ratio of ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 0.670 +/- 0.166**, 0.677 +/- 0.194**, 0.721 +/- 0.178, respectively (**: p < 0.01 vs. delayed DP-Tl SPECT images). Systolic blood pressure fell at 11 min after ACZ infusion without electrocardiographic ST-T changes or chest pain. CONCLUSION: As ACZ has the potential to cause myocardial ischemia, ACZ-augmented brain SPECT should be performed with caution in patients with severe coronary artery disease associated with cerebrovascular disease.

Acetazolamide↗

PubMed1998

Suppression of male-specific cytochrome P450 isoforms by bisphenol A in rat liver.

We examined the effect of bisphenol A (BPA) on microsomal cytochrome P450 (P450) enzymes in rats. Rats were treated intraperitoneally with BPA daily for 4 days, at doses of 10, 20, and 40 mg/kg. Among the P450-dependent monooxygenase activities, testosterone 2alpha-hydroxylase (T2AH) and testosterone 6beta-hydroxylase (T6BH) activities, which are associated with CYP2C11 and CYP3A2 respectively, were remarkably decreased by 40 mg/kg BPA. The levels of the control activities were 13 and 50%, respectively. Furthermore, immunoblotting showed that BPA (20 or 40 mg/kg) significantly reduced CYP2C 11/6 and CYP3A2/1 protein levels in rat liver microsomes. In addition, estradiol 2-hydroxylase (ED2H) and benzphetamine N-demethylase (BZND) activities were significantly decreased by BPA at 20 and 40 mg/kg (by 19-73%). The Km values for T2AH and T6BH in 20 and 40 mg/kg BPA-treated rats were significantly high compared with that in control rats. The Vmax for T2AH was dose-dependently decreased by BPA treatment, whereas that of T6BH was only decreased by BPA at 40 mg/kg. On the other hand, lauric acid omega-hydroxylase (LAOH) activity was significantly increased by BPA at 20 and 40 mg/kg (1.5- and 1.7-fold, respectively). Immunoblot analysis showed that 20 and 40 mg/kg BPA induced CYP4A1/2 protein expression. However, the activities 7-ethoxyresorufin O-deethylase (EROD), 7-methoxyresorufin O-demethylase (MROD), 7-ethoxycoumarin O-deethylase (ECOD), 7-benzyloxyresorufin O-debenzylase (BROD), aminopyrine N-demethylase (APND), chlorzoxazone 6-hydroxylase (CZ6H), erythromycin N-demethylase (EMND), and testosterone 7alpha-hydroxylase (T7AH) were not affected by BPA at any dose. These results suggest that BPA affects male-specific P450 isoforms in rat liver, and that these changes closely relate to the toxicity of BPA.

Animals↗

PubMed1998

Assessment of reperfused myocardium using a new ischaemia-avid imaging agent, technetium-99m HL91: comparison with myocardial glucose uptake.

We evaluated the efficacy of a new ischae-mia-avid imaging agent, technetium-99m labelled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (99mTc- HL91) as a marker of myocardial viability in ischaemic and reperfused myocardium. The left coronary artery of rats was ligated for 15 or 60 min and released. The myocardium was reperfused for 60 min [stunned myocardium, or acute myocardial infarction (MI)] or 7 days (subacute MI). Thereafter, 99mTc-HL91 and carbon-14 2-deoxyglucose (DG) were co-injected 30 min before sacrifice. We evaluated the myocardial accumulation of 99mTc-HL91 and DG by dual-tracer ex vivo autoradiography. The uptake of each tracer in the myocardial region was normalized by that in the septum (control), and expressed as percent uptake (%HL or %DG, respectively). Individual hearts were also histopathologically examined. The %HL in the stunned myocardium (n = 8) and in the septum were identical (101%+/-15%, mean+/-SD, P = ns), whereas the %DG was significantly increased (149%+/-27%, P<0.05) compared with that in the septum. These results suggest that 99mTc-HL91 cannot visualize stunned myocardium, whereas DG can. In acute MI (n = 7), the %HL (423%+/-96%, P<0.005) and the %DG (318%+/-91%, P<0.001) in the non-infarcted area at risk were significantly augmented compared with those in the septum. The %DG (181%+/-17%) in the infarcted area was also augmented (P<0.001), whereas the %HL (106%+/-25%) in the infarcted area was identical to that in the septum (P = ns). These results indicate that 99mTc-HL91 detected viable myocardium in the area at risk. In subacute MI (n = 8), the%HL in the infarcted area (101%+/-45%) and in the septum was identical, whereas %DG (292%+/-57%) was significantly higher than that in the non-infarcted risk area or the septum (P<0.0001). These findings suggest that DG detected viable myocardium in the area at risk, but that 99mTc-HL91 was not retained. We conclude that 99mTc-HL91 is a potent marker of myocardial viability when used during the early acute phase after reperfusion.

Animals↗

PubMed1998

Structure of neutral branched xylooligosaccharides produced by xylanase from in situ reduced hardwood xylan.

Two neutral oligosaccharides from in situ reduced hardwood xylan were isolated and completely characterized by methylation analysis and 2D NMR spectroscopy (COSY, HOHAHA, HMQC, HMQC-TOCSY, NOESY, and HMBC techniques). The oligosaccharides are the xylotetrasaccharide, 4-O-methyl-alpha-D-glucopyranosyl-(1-->2)-D-xylotriose and the xylopentasaccharide 4-O-methyl-alpha-D-glucopyranosyl-(1-->2)-D-xylotetraose. From reactivities observed with these compounds, the mode of action of beta-xylanase is described.

Carbohydrate Sequence↗