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Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 451 records · Page 25Linked to original sources
PubMed1996

Inhibition of GABAA receptor chloride channel by quinolones and norfloxacin-biphenylacetic acid hybrid compounds.

Receptor binding studies have shown that the combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, inhibits GABAA receptors. In order to elucidate further the mechanism of these drug interactions, the effect of quinolone antibacterial agents on muscimol-stimulated 36Cl- uptake in rat cerebral cortical synaptoneurosomes was investigated in the absence or presence of BPAA. In the absence of BPAA, quinolones such as norfloxacin (NFLX) and enoxacin attenuated muscimol-stimulated 36Cl- uptake at 10 microM and above. In combination with 10 microM BPAA, the inhibitory effect of these drugs was potentiated and there was a parallel shift of the inhibition curves to the left for these drugs. BPAA alone (1 and 10 microM) did not affect basal or muscimol-stimulated 36Cl- uptake. Hybrid molecules of NFLX and BPAA were synthesized and their inhibitory potency was also investigated. Inhibition curves of muscimol-stimulated 36Cl- uptake revealed that a hybrid with a -CONH(CH2)3- chain between NFLX and BPAA (flexible structure) (1 nM-20 microM) inhibited muscimol-stimulated 36Cl- uptake more potently than did the combination of NFLX (10 nm-100 microM) and 10 microM BPAA. In contrast, another hybrid linked by -CONH-(stretched structure) exhibited a weak inhibitory effect at 10 microM. These results suggest that quinolones in combination with BPAA bind to GABAA receptors, thus inhibiting Cl- channel activity, and that the inhibitory potency of quinolones may be enhanced by an intermolecular interaction with BPAA.

Animals↗
PubMed1996

PET imaging of primary mediastinal tumours.

Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours.

Adolescent↗
PubMed1996

G2 arrest following fractionated irradiation in the mouse jejunal crypt.

A G2 block is a well-known response to irradiation, showing a delay time that depends on the given single dose. Our question was whether the division delay time is the same after multiple doses as after a single dose. We therefore studied mitosis in the mouse jejunal crypt using a quantitative approach. Three radiation schedules with a fraction size of 2 Gy were compared: a single dose and twice-daily irradiation at a 4-h interval, for 1 or 3 days. With the single dose, mitotic figures disappeared at 0.5 h and reappeared after 2 h. At the end of each multiple-dose regimen, significant numbers of mitoses could be observed at 0.5 and 1 h but a trough was seen at 2 h, with numbers then increasing again. Calculated average division delays after the single dose and repeated doses for 1 and 3 days were 1.5, 1.3 and 1.7 h respectively. In summary, most crypt cells treated with multiple fractions remain susceptible to G2 arrest, showing the same delay time as with the single dose.

Animals↗
PubMed1996

Anatomical configuration of the spinal column in the supine position. III. Comparison of adolescent and adult volunteers.

To clarify the anatomical configuration of the spinal column in the adolescent in the supine position, we have studied 10 adolescent (13-17 yr) and 10 adult (26-38 yr) volunteers using magnetic resonance imaging. T1-weighted sagittal midline magnetic resonance images of the spinal column were obtained with subjects in the supine position. The maximum angles of decline of the lumbar spinal canal did not differ between the adolescent (mean 13.6 (SD 3.3) degrees) and adult (12.4 (3.8) degrees) groups. The maximum angles of incline of the upper thoracic spinal canal were smaller in the adolescent group (15.9 (4.7) degrees) than in the adult group (26.4 (5.8) degrees). The median highest point of the lumbar spinal canal was located at L4 (range L3-4 to L4-5) in both groups. The lowest points of the thoracic spinal canal in the adolescent and adult groups were located at T8-9 (T7 to T9) and T8 (T6-7 to T9), respectively. This study showed that thoracic kyphotic curvature in adolescents was reduced significantly in the supine position compared with that in adults. This minimized thoracic kyphosis may explain, in part, the enhanced cephalad spread of subarachnoid hyperbaric anaesthetic solutions in adolescents.

Adolescent↗
PubMed1996

Soft tissue anatomy within the vertebral canal in pregnant women.

To clarify pregnancy-induced changes in soft tissue anatomy within the vertebral canal, we have studied magnetic resonance (MR) images of the lumbar spine in three women. In each subject, T2-weighted axial MR images were obtained both before pregnancy and at 32 weeks' gestation, and the paired images were compared. The extradural venous plexus was engorged significantly in supine parturients. In addition, the engorged extradural venous plexus displaced the dura away from the wall of the vertebral canal in a posterior direction, which resulted in a decrease in the volume of the cerebrospinal fluid in the dural sac. These findings confirmed the long-held concept that the engorged extradural venous plexus in supine parturients decreases the effective capacity of the extradural and subarachnoid spaces.

Adult↗
PubMed1996

Inflammatory changes after extradural anaesthesia may affect the spread of local anaesthetic within the extradural space.

We have assessed cephalad spread of analgesia in 491 patients undergoing extradural anaesthesia at the L2-3 or L3-4 interspace. Patients were classified into one of three groups based on the number of previous lumbar extradural anaesthesia procedures: none (group I, n = 339), one (group II, n = 82), and two or more (group III, n = 70). Cephalad spread of analgesia was greater in group I than in groups II and III, regardless of the puncture site. In addition, we examined the extradural space using a flexible extraduroscope in 32 patients who were excluded from the analysis of spread. Extraduroscopy showed the extradural space to be patent in patients with no history of prior lumbar extradural anesthesia, but it was not clearly identified in patients who had received extradural anaesthesia one or more times because of aseptic inflammatory changes, including proliferation of connective tissue, adhesions between the dura mater and the ligamentum flavum, granulation and changes in the ligamentum flavum. Extradural anaesthesia may cause aseptic inflammatory changes in the extradural space which may reduce the spread of analgesia.

Adult↗
PubMed1996

Acid-base state of cerebrospinal fluid during pregnancy and its effect on spread of spinal anaesthesia.

To assess the possible relationship between changes in acid-base state of cerebrospinal fluid (CSF) and enhanced spread of spinal anaesthesia during pregnancy, we have measured CSF pH, carbon dioxide tension (PCO2) and HCO3- values in 73 women undergoing spinal anaesthesia with hyperbaric amethocaine 8 mg. Patients were allocated to one of four groups according to gestational period: non-pregnant group (n = 13), first trimester group (8-13 weeks, n = 19), second trimester group (14-26 weeks, n = 11) and third trimester group (27-39 weeks, n = 30). The pH of the CSF was greater in the second and third trimester groups than in the non-pregnant group. CSF PCO2 decreased by 0.53-0.8 kPa throughout pregnancy. CSF HCO3- was decreased throughout pregnancy. Overall, no clinically significant correlation was found between maximum cephalad spread of analgesia and CSF pH, PCO2 or HCO3-. We conclude that pregnancy-induced changes in acid-base state of CSF have little effect on the spread of spinal anaesthesia, although there is a clinically different spread of spinal anaesthesia between non-pregnant and pregnant states.

Acid-Base Equilibrium↗
PubMed1996

Soybean protein suppresses hepatic lipogenic enzyme gene expression in Wistar fatty rats.

The effects of dietary soybean protein on lipogenic enzyme gene expression in livers of genetically fatty rats (Wistar fatty) have been investigated. When Wistar fatty rats and their lean littermates (7-8-wk old) were fed a casein or soybean protein isolate diet containing hydrogenated fat (4% hydrogenated fat plus 1% corn oil) or corn oil (5%) for 3 wk, the hepatic messenger RNA concentrations and activities of lipogenic enzymes were significantly lower in rats fed soybean protein than in those fed casein, regardless of genotype or dietary fat. The conversion rates of thyroxine to triiodothyronine by liver microsomes and plasma triiodothyronine concentrations were lower in the fatty rats than in the lean rats and were significantly greater in rats fed soybean protein than in those fed casein. Conversely, plasma and liver triacylglycerol concentrations were lower in soybean protein-fed fatty and lean rats than in those fed casein. The body weight was less in the fatty rats fed soybean protein than in those fed casein after 3 wk of feeding. Moreover, dietary polyunsaturated fatty acids suppressed lipogenic enzyme gene expression in the lean rats but did not in the fatty rats. Dietary soybean protein appeared to be useful for the reduction of obesity.

ATP Citrate (pro-S)-Lyase↗
PubMed1996

Cytochrome P450rm from Rhodotorula minuta catalyzes 4-hydroxylation of benzoate.

Rhodotorula minuta, a red yeast, produces a cytochrome P450, tentatively named P450rm, catalyzing the formation of isobutene from isovalerate. We found that P450rm interacted with benzoate and the dissociation constant of P450rm for benzoate was 36 microM. A reconstituted system that consisted of purified P450rm and cytochrome P450 reductase catalyzed the 4-hydroxylation of benzoate in addition to the formation of isobutene; the turnover rate was approximately 40 nmol/min/nmol P450rm. The P450rm-monooxygenase system was specific for benzoate and did not catalyze hydroxylation of other aromatic carboxylates. Since only a benzoate 4-hydroxylase that requires tetrahydropteridine has been isolated to date, P450rm appears to be the first isolated cytochrome P450 that acts as a benzoate 4-hydroxylase. The P450rm-monooxygenase system in microsomes of R. minuta might function in the degradation of L-phenylalanine on the pathway to beta-ketoadipate.

Adipates↗
PubMed1996

Nutritional regulation of lipogenic enzyme gene expression in rat epididymal adipose tissue.

The time courses of gene expression, and the nutritional regulation of gene expression of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase, ATP citrate-lyase, malic enzyme, and glucose-6-phosphate dehydrogenase) in epididymal adipose tissue after refeeding food-deprived rats have been investigated and compared with those in liver (previously reported). The mRNA concentrations of lipogenic enzymes reached maximum levels at 24 h after the refeeding in adipose tissue and at 8-16 h in liver, while the enzyme induction reached maximum at 48-72 h in both tissues. Moreover, the mRNAs were more strongly induced in adipose tissue than in liver, whereas the enzyme induction (except malic enzyme) was lower. In adipose tissue of rats fed a carbohydrate diet without protein, the mRNA concentrations of acetyl-CoA carboxylase, ATP-citrate lyase, malic enzyme, and fatty acid synthase reached comparable levels to those of the carbohydrate/protein diet group. The protein feeding increased the enzyme induction in adipose tissue. As regards reduction of gene expression, lipogenic enzyme mRNA concentrations were not so markedly reduced by starvation or polyunsaturated fatty acids in adipose tissue as in liver. The differences in regulation of lipogenic enzyme gene expression and induction between adipose tissue and liver can be ascribed to tissue specificity.

ATP Citrate (pro-S)-Lyase↗
PubMed1996

An early phase II study of etoposide (VP-16) in advanced gastric cancer.

An early phase II study was conducted to evaluate the anti-tumor effects and toxicity of etoposide in patients with unresectable or relapsed advanced gastric cancer. From April 1991 to December 1992, 13 patients were enrolled into this study; one was subsequently considered ineligible. Before enrollment, all the patients had been treated with chemotherapy which did not include etoposide. Etoposide (100 mg/m2/day) was administered as an intravenous infusion over 120 min for five consecutive days and was repeated every four weeks. Seven patients received one course of this therapy and the remaining five received two. No patient showed a complete or a partial response. No change and progressive disease were observed in three and nine patients, respectively. The clinical toxicities (grade 3-4; WHO) of leukocytopenia, anemia and alopecia occurred in 50, 42, and 42% of the patients, respectively. We conclude that this dose of etoposide administered according to the present schedule is ineffective in previously treated patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed1996

Prognostic value of histopathological therapeutic effects and mitotic index in locally advanced breast cancers after neoadjuvant chemotherapy.

A study was conducted to examine whether or not the histopathological therapeutic effects of preoperative chemotherapy could be useful for determining prognosis in women with locally advanced breast cancer. The patients were 37 women with locally advanced breast cancer who received preoperative chemotherapy between 1977 and 1987. The histological grade of malignancy (HGM) and histopathological therapeutic effects of chemotherapy (TEf) were examined in resected specimens. Patients with HGM 3 showed a poorer 10-year overall survival (38%) than those with HGM 1 or 2 (62%). Patients showing a better histopathological response (TEf 1b plus 2) had a poorer 10-year overall survival (20%) than those with a poorer response (TEf 0 plus 1a) (60%). Therapeutic effects were significantly related to histological grade, nuclear atypia and mitotic index (p = 0.03, 0.005 and 0.002, respectively). Histopathological therapeutic effects were not directly correlated with patient prognosis. Cox proportional hazard regression analysis revealed that mitotic index was the most significant prognostic factor related to 10-year overall survival.

Adult↗
PubMed1996

Differential expression of three genes for different beta-tubulin isotypes during the initial culture of Zinnia mesophyll cells that divide and differentiate into tracheary elements.

Complementary DNA clones for three different beta-tubulin isotypes (ZeTubB1, ZeTubB2 and ZeTubB3) were isolated from a cDNA library generated from RNA of cultured mesophyll cells of Zinnia elegans that were differentiating into tracheary elements and/or dividing. Sequence analysis revealed that the proteins encoded by ZeTubB1 and ZeTubB3 and that encoded by ZeTubB2 were each homologous to two of three groups of beta-tubulin isotypes in Arabidopsis. RNA gel blot analysis of the expression of the ZeTubB transcripts indicated that transcripts that corresponded to each clone were differently expressed during culture of Zinnia mesophyll cells. In particular, the level of expression of ZeTubB1 and ZeTubB3 transcripts increased rapidly prior to cell division and secondary wall formation, and such expression was promoted by combinations of auxin and cytokinin that induced tracheary element differentiation as well as cell division. Results of an in situ hybridization experiment with an antisense RNA probe derived from ZeTubB1 cDNA suggested the preferential expression of ZeTubB transcripts in differentiating xylem cells, as well as in the ground meristem and the procambium, of Zinnia seedlings.

Amino Acid Sequence↗
PubMed1996

Dedifferentiated liposarcoma of the subcutis.

This report describes an 82-year-old woman with dedifferentiated liposarcoma, an extremely rare neoplasm of the subcutis. The patient had first recognized a very soft mass in the anterolateral part of the right thigh more than 20 years earlier, but because the tumor showed little change over this period, she did not seek treatment. She recently noticed a hard, rapidly growing mass within the former tumor. Both magnetic resonance imaging and axial computed tomography revealed a subcutaneous fatty lesion measuring 12 x 7 x 4 cm and a well-delineated mass-like area (4 x 3 x 3 cm) of nonfatty tissue within the lesion. Histologically, the former was a mature lipomatous tumor with broad fibrous septa containing some atypical stromal cells, and the latter was a much more cellular, spindle cell tumor with a malignant fibrous histiocytoma-like pattern. The authors propose that dedifferentiated liposarcoma is not restricted to the deep soft tissues and may develop in the subcutis and further suggest appropriate surgical management for well-differentiated fatty tumors of subcutaneous origin.

Aged↗
PubMed1996

Sevoflurane is equivalent to isoflurane for attenuating bupivacaine-induced arrhythmias and seizures in rats.

The effects of sevoflurane on bupivacaine toxicity have not been defined. The purpose of this study was to investigate the effects of sevoflurane and isoflurane on bupivacaine-induced arrhythmias and seizures in rats. Thirty-seven Sprague-Dawley rats received bupivacaine intravenously at a constant rate of 2 mg.kg-1.min-1 until both arrhythmias and seizures occurred while electrocardiogram (ECG) and electroencephalogram (EEG) recordings were made. The cumulative doses of bupivacaine inducing arrhythmias and seizures were determined in the presence of 1 minimum alveolar anesthetic concentration (MAC) of sevoflurane (sevoflurane group, n = 14) or isoflurane (isoflurane group, n = 10) and in the absence of anesthetic (control group, n = 13). The cumulative doses of bupivacaine inducing arrhythmias and seizures were larger in the sevoflurane and isoflurane groups than in the control group and were similar in the sevoflurane and isoflurane groups. These results indicate that sevoflurane and isoflurane attenuate bupivacaine-induced arrhythmias and seizures in rats.

Anesthetics, Inhalation↗
PubMed1996

Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide.

RATIONALE AND OBJECTIVES: The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. METHODS: Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. RESULTS: The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. DISCUSSION: The increase in frequency of SCE seen after the addition of Gd-DTPA was decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related.

Cells, Cultured↗
PubMed1996

A multicenter validation of regional cerebral blood flow quantitation using [123I]iodoamphetamine and single photon emission computed tomography.

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function. The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54x) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects: y = 2.0 + 0.80x). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55x). Mean cortical gray matter rCBF in a group of normal subject was 43.9 +/- 3.3 and 43.4 +/- 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml +/- 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = -3.21 + 1.07x, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

Adolescent↗