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Biomedical subjects

Y Okuno

Publications and source records attributed to Y Okuno.

At least 109 records · Page 6Linked to original sources
PubMed1995

Pyrethroids, nerve poisons: how their risks to human health should be assessed.

The extensive worldwide efforts of structural modification of natural pyrethrins for better performances have resulted in successful development of a wide variety of synthetic pyrethroids with tremendously high efficacy, knock-down activity or vapor action, and/or with acceptable environmental stability and safety. Currently these pyrethroids including their preferentially manufactured stereoisomers are widely used in agriculture, and for public health as well as household insect control. The detailed toxicology and metabolism studies intended to attain human risk assessment have revealed that with voltage-dependent sodium channel as target site pyrethroids induce pronounced repetitive activity characterized grossly by tremor, hypersensitivity, choleoathetosis, and salivation. In addition, so-called cyano-pyrethroids cause transient skin paresthesia in workers. With regard to tumorigenicity, mutagenicity, teratogenicity and developmental toxicity, no significant findings have been reported. Pyrethroids are eliminated from the animals quite rapidly and completely, undergoing oxidation and ester hydrolysis followed by various conjugations, with low tissue residues. Thus, overall, sound scientific bases exist for human risk assessment under the present usage conditions.

Animals↗
PubMed1995

Syntheses, immunosuppressive activity, and structure-activity relationships of myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxyomyriocin, and nor-deoxomyriocins.

Nine myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxomyriocin, and nor-deoxomyriocins, were synthesized from 2-deoxy-D-glucose via common intermediates used in previous myriocin and Z-myriocin syntheses. Immunosuppressive activities of those myriocin analogs on mouse allogeneic mixed lymphocyte reaction were examined, and Z-14-deoxomyriocin was found to show the most potent activity among them. The structure-activity relationships are discussed.

Animals↗
PubMed1995

Impaired retinal artery blood flow in IDDM patients before clinical manifestations of diabetic retinopathy.

OBJECTIVE: To determine whether hemodynamic changes in retinal arteries precede clinical manifestations of diabetic retinopathy and to examine the effects of control of hyperglycemia on retinal artery blood flow. RESEARCH DESIGN AND METHODS: We assessed blood flow in bilateral central retinal arteries in 50 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 20 sex- and age-matched control subjects using duplex Doppler sonography. We determined the peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged velocity (TAV), resistance index (RI), and pulsatility index (PI). RESULTS: PSV, EDV, and TAV were significantly lower in IDDM patients than in control subjects (P < 0.05, P < 0.01, and P < 0.01, respectively). The RI was significantly higher in IDDM patients than in control subjects (P < 0.01) and was significantly correlated with plasma levels of glucose in IDDM patients (r = 0.0.310, P = 0.0248). Multiple regression analysis identified the plasma levels of glucose as a significant determination of RI in IDDM patients. After 14 days of intensive insulin therapy in 7 IDDM patients, the RI and plasma levels of glucose showed significant decreases (P = 0.018, P = 0.001, respectively). CONCLUSIONS: Our results showed that changes in retinal hemodynamics were present before the clinical detection of overt diabetic retinopathy and suggest that the presence of short-term hyperglycemia partly contributes to impaired retinal circulation.

Adolescent↗
PubMed1995

Clinical results of breast-conservation therapy using a CT simulator.

The CT simulator is a real-time, CT-linked, 3-D treatment planning system which consists of a CT scanner, a multi-image display, a treatment planning device with real-time visual optimization, and a laser beam projector. The clinical benefit of this system was evaluated in breast cancer patients undergoing breast-conserving therapy. Between December 1987 and March 1993, 244 breasts in 243 patients underwent breast-conserving therapy at Kyoto University Hospital. Clinically, there were 159 stage I and 85 stage II tumors. Pathological staging showed 216 stage I, 24 stage II, and 4 stage III tumors. All except 10 tumors were invasive ductal carcinomas. Eleven tumors were margin-positive by histopathological examinations. As surgical treatment, quadrantectomy or wide excision with complete axillary dissection was performed. Radiation therapy consisted of 50 Gy delivered to the whole breast by opposed tangential fields over 5 weeks using 60Co gamma rays. For patients with a positive margin, boost electron irradiation was given to a total of 10 Gy. We used the CT simulator for individualized optimization of the tangential fields. Prompt and accurate determination of the tangential portals was possible by using the simulator to determine various parameters, including the beam angle and head rotation angle. During follow-up for 2-66 months (median: 20 months), unrelated death occurred in 2 patients and distant metastases developed in 5 (bone 4, lung 1). However, neither local recurrence nor symptomatic radiation pneumonitis has since occurred. The cumulative survival rate and the disease-free survival rate at five years were 95.2% and 91.8%, respectively. The CT simulator appears to be a useful tool for individualized optimization of tangential irradiation fields in breast-conserving therapy.

Adult↗
PubMed1995

[Recent progress of thermoradiotherapy in cancer therapy].

The recent progress of thermoradiotherapy for cancer is reviewed. Several biological methods for increasing the effects of heat on tumors have been developed, and some of them are being clinically investigated. Physical progress includes two new heating devices developed in Japan. One is an ultrasound heating system and the other is an intracavitary RF heating applicator in which simultaneous intracavitary irradiation is possible. The negative results of RTOG trial in USA caused a great impact in clinical hyperthermia. Careful analysis of this trial, however, demonstrated the advantages of the use of hyperthermia for those cases in which ther was good quality assurance of hyperthermia. Recent results of ESHO trials in Europe clearly demonstrated the superiority of thermoradiotherapy over radiotherapy alone for several tumors. Various site-specific clinical trials are expected to clarify the indications of thermoradiotherapy in future.

Clinical Trials, Phase III as Topic↗
PubMed1995

[The efficacy of midazolam-famotidine suppository for premedication in children].

We evaluated the efficacy of midazolam-famotidine suppository (M-F suppository) for premedication in children. After obtaining informed parental consent, we studied children aged 5m-7y, ASA I status, scheduled for minor elective surgery. The suppository group (n = 26) was given suppository of both midazolam 0.5 mg.kg-1 and famotidine 2 mg.kg-1, and the intramuscular injection group (n = 19) was given hydroxyzine 1 mg.kg-1. In the suppository group, gastric pH (3.90 +/- 0.34) was significantly higher, and gastric volume (1.88 +/- 0.54 ml) was significantly less than in the intramuscular injection group (1.82 +/- 0.15, 8.42 +/- 1.76 ml). The M-F suppository may offer similar sedative effect as an intramuscular injection of hydroxyzine. We concluded that the M-F suppository is an effective premedicant for pediatric patients.

Administration, Rectal↗
PubMed1995

Rerupture of cerebral aneurysms during angiography.

PURPOSE: To assess the incidence of angiography-related rerupture of intracranial aneurysms and to analyze other risk factors of this complication. METHODS: Clinical data from 144 patients with acute subarachnoid hemorrhage from ruptured intracranial aneurysm were reviewed retrospectively. In all patients, angiography was done by the transaortic approach. RESULTS: The incidence of rerupture caused by angiography was 2 (1.4%) of 144 and that of spontaneous rerupture was 14 (9.7%) of 144. Angiography within 6 hours after the initial subarachnoid hemorrhage attack was associated with a significantly higher incidence of rerupture (4.8%) than that after a longer interval (0%). In cases of spontaneous rerupture, patients with worse levels of consciousness showed a higher incidence of rerupture, and this tendency also was evident in cases of induced rerupture. There was no significant correlation between the rerupture rate and the injection volume of contrast medium, aneurysm location, or patient age or sex. CONCLUSION: Although angiography within 6 hours after initial intracranial aneurysm rupture was associated with a higher rate of rerupture, the incidence of rerupture in this study (4.8%) was much lower than those reported previously (20% to 38.5%). The present findings suggest that emergency angiography within 6 hours after aneurysm rupture, which enables neurosurgeons to carry out early surgery, should not be discouraged.

Aged↗
PubMed1995

Personality deviation and gastric motility in patients with functional dyspepsia.

We studied gastric motor functions by scintigraphic gastric emptying analysis and surface electrogastrography (EGG), and personality trait deviation in patients with functional dyspepsia. Delayed gastric emptying was observed in 17/35 patients and reduced normal EGG activity in 22/35 functional dyspepsia patients. There was a highly significant negative correlation between the gastric retention rate (at 150 min) and the duration of normal EGG waves. Abnormally high T scores on the Minnesota Multiphasic Personality Inventory (MMPI) test (70 or above) were found in 14/21 patients. Hypochondriasis (Hs) and conversion hysteria (Hy) were the most common abnormal findings. Ninety percent of functional dyspepsia patients (19/21) had either gastric dysmotility and/or psychological deviation. Although there was no significant correlation between gastric dysmotility and deviation in personality traits in functional dyspepsia patients, these data suggest that brain-gut interactions may play an important role in the symptoms of functional dyspepsia.

Adolescent↗
PubMed1994

Computer modeling analysis for enediyne chromophore-apoprotein complex of macromolecular antitumor antibiotic C-1027.

On the basis of the van der Waals and electrostatic potential energy calculations and energy minimization (EM), a model for the apoprotein-chromophore complex of C-1027 has been constructed by docking the apoprotein (Apo-C1027) and the chromophore (C1027-Chr). The model of the apoprotein-chromophore complex also suggests the most probable stereochemistry of the chromophore (8R,9S,13R,17R), specific interactions between Apo-C1027 and C1027-Chr, and the origin of the stabilization of the chromophore by the apoprotein. The acetylenic bond of C1027-Chr appears to be stabilized by (1) hydrophobic interactions with the bottom of the pocket of Apo-C1027, (2) orbital interaction with Cys36-Cys45 disulfide bond, (3) van der Waals contact with Pro76, and (4) pi-pi stacking with the benzene moiety of the chromophore. In this model, molecular dynamics (MD) simulation of the chromophore indicates that the acetylene bond distance (C2-C7) of the apoprotein-bound chromophore is longer than that of the unbound chromophore.

Amino Acid Sequence↗
PubMed1994

Production of parathyroid hormone-related protein by cultured human myeloma cells.

We examined whether or not parathyroid hormone-related protein (PTH-rP) is produced in cultured human myeloma cells. PTH-rP protein was detected in the cell extract of one (U266) of 6 myeloma cell lines examined by radioimmunoassay. Also we demonstrated the expression of PTH-rP mRNA in all of the 6 lines. These findings indicate that PTH-rP may be one of the factors responsible for the bone destruction or hypercalcemia in multiple myeloma.

Base Sequence↗
PubMed1994

Lack of induction of epithelial cell proliferation by sodium saccharin and sodium L-ascorbate in the urinary bladder of NCI-black-Reiter (NBR) male rats.

The susceptibility to induction of epithelial cell proliferation by three urinary bladder cancer promoters was investigated in NCI-Black-Reiter (NBR) rats, which lack alpha 2u-globulin-synthesizing ability. Six-week-old male NBR and F344 rats were given 5% sodium saccharin (Na-Sac), 5% sodium L-ascorbate (Na-AsA), or 3% uracil in the basal diet for 8 weeks. Administration of uracil evoked a marked cell proliferation response and papillomatosis associated with calculus formation in NBR as well as F344 rats. This result indicates that NBR rats are also susceptible to direct mechanical stimulation. In contrast, both strains of rats given Na-Sac or Na-AsA demonstrated an alkalization of urinary pH and an increase in urinary Na ion concentration, but increase in cell proliferation in the urinary bladder transitional epithelium was only observed in F344 rats. Since previous studies revealed that elevation of urinary pH and Na ion concentration are essential factors for exertion of promotion activity by Na-Sac and Na-AsA, the results of the present investigation suggest that alpha 2u-globulin might also be a necessary component of the mechanisms of their promotion of male rat urinary bladder carcinogenesis.

Animals↗
PubMed1994

The correlation of serum luteinizing hormone levels with the induction of Leydig cell tumors in rats by oxolinic acid.

Studies were performed to examine the mechanism by which testicular Leydig cell tumors are induced in rats by administration of the antimicrobial agent oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid). In these studies, the effects of oxolinic acid on serum levels of luteinizing hormone (LH), testosterone, and prolactin and the binding of testosterone to prostatic androgen receptors were examined. In a long-term hormonal study, male Wistar rats were fed a diet containing oxolinic acid at 0, 100, 1000, or 3000 ppm for 104 weeks. A statistically significant increase in serum LH levels was observed at 1000 and 3000 ppm, but no dose of oxolinic acid had a significant effect on serum testosterone levels. Serum LH levels were no longer elevated above control levels within 2 weeks of cessation of the administration of oxolinic acid. Oxolinic acid was found to have no effect on the rate of clearance of exogenous LH from the circulation. Serum prolactin levels were decreased by the administration of oxolinic acid. The increase in serum LH induced by oxolinic acid was completely blocked by the intraperitoneal injection of the dopamine antagonist haloperidol (2 mg/kg). In addition, no significant affinity of oxolinic acid for androgen receptors was found in an in vitro study. These findings suggest that: (1) oxolinic acid induces Leydig cell tumors in rats by chronically stimulating the release of LH from the pituitary, (2) the mechanism of stimulating the release of LH involves facilitation of the dopaminergic systems in the hypothalamus-pituitary axis, and (3) oxolinic acid has no effect on androgen-mediated feedback inhibition.

Administration, Oral↗
PubMed1994

Antroduodenal motility and transpyloric fluid movement in patients with diabetes studied using duplex sonography.

BACKGROUND/AIMS: To elucidate the relationship between diabetic autonomic neuropathy and gastrointestinal motility, antroduodenal motility was studied in patients with diabetes using duplex sonography. METHODS: Antroduodenal motility, transpyloric fluid movement, and velocity curves of fluid flow were studied using duplex sonography in 32 patients with diabetes and 10 healthy subjects after their ingestion of a meat soup. RESULTS: The frequency of antroduodenal coordination was significantly reduced in patients with diabetes with both early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency and duration of end-cycle reflux episodes were also significantly reduced in patients with early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency of end-cycle reflux episodes was closely correlated with the frequency of antroduodenal coordination in both healthy subjects (r = 0.859; P = 0.002) and patients with diabetes (r = 0.929; P = 0.0001). There was a significant correlation between fasting plasma glucose concentrations and the frequency of antroduodenal coordination in patients with diabetes (r = -0.361; P = 0.039). CONCLUSIONS: These findings suggest that reduced frequency and duration of end-cycle reflux episodes may be an early indicator of diabetic gastroparesis that may be related mainly to autonomic neuropathy but also in part to acute hyperglycemia.

Adult↗
PubMed1994

Carcinogenicity studies of oxolinic acid in rats and mice.

A chronic feeding study was conducted to determine the carcinogenic potential of oxolinic acid, an antimicrobial agent, in rats and mice. Oxolinic acid was administered in the diet to Wistar rats (0, 30, 100, 300 or 1000 ppm; 50 rats/dose/sex) for 104 wk and to ICR mice (0, 50, 150 or 500 ppm; 50 mice/dose/sex) for 78 wk. Clinical signs, body weight, food consumption, autopsy findings and histopathological data were noted. Mortality was unaffected by oxolinic acid administration in neither species. In rats, body weight gain was suppressed in both sexes at 1000 ppm. Histopathological examinations conducted after autopsy at 104 wk revealed a slight increase in benign Leydig cell tumours of the testis at 1000 ppm, which did not appear until late in the lifetime of rats. No other treatment-related neoplastic lesions were observed in rats. Non-neoplastic lesions in males at 1000 ppm included Leydig cell hyperplasia and tubular atrophy of the testes. In mice, decreased body weight gain was observed in both sexes at 500 ppm, but no non-neoplastic or neoplastic lesions attributable to the treatment with oxolinic acid occurred in either sex. In conclusion, oxolinic acid induced benign Leydig cell tumours of the testis in rats at the highest dose level tested (1000 ppm). The no-effect level for tumour induction was confirmed to be 300 ppm (10.9 mg/kg/day) in rats. None was induced in mice.

Animals↗
PubMed1994

Complementation of xeroderma pigmentosum cells by microinjection of mRNA fractionated under denaturing conditions: an estimation of sizes of XP-E and XP-G mRNA.

Excision repair deficiencies in groups A and G xeroderma pigmentosum (XP) cells are transiently complemented after microinjection of HeLa poly(A)+RNA, but those in groups D and F are not complemented (Legerski et al., 1984). We tested XP cells belonging to the seven complementation groups, A-G, and Cockayne's syndrome (CS) cells belonging to the two complementation groups, A and B, for transient correction by microinjection of total poly(A)+RNA from HeLa cells. Among the XP cells, unscheduled DNA synthesis (UDS) was increased only in XP-A cells by microinjection of total poly(A)+RNA. However, UDS was increased in XP-E and XP-G cells as well as in XP-A cells by microinjection of concentrated poly(A)+RNA fractionated on a 5-25% sucrose density gradient containing methylmercuric hydroxide. The sizes of XP-E and XP-G mRNA were estimated to be 1.5-2.7 kb and 2.0-3.8 kb, respectively, by comparison to internal marker RNAs including 18S rRNA, 28S rRNA, HPRT mRNA and XPAC mRNA. RNA synthesis recovery after UV exposure in CS cells was not increased by microinjection of either total poly(A)+RNA or fractionated RNA. These results provide estimates of the sizes of XP-E and XP-G proteins and will facilitate molecular cloning of DNA repair genes, especially of XP-E and XP-G genes.

Centrifugation, Density Gradient↗
PubMed1994

An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum.

We have isolated a human excision repair gene ERCC5 which complements the defect of the mouse UV-sensitive mutant XL216 (rodent complementation group 5). Here we report cDNA cloning of human and mouse ERCC5 genes using an exon containing an ERCC5 fragment as a probe. The ERCC5 cDNA encodes a predicted 133-kDa nuclear protein that shares some homology with the product of the yeast DNA repair gene RAD2. Transfection with mouse ERCC5 cDNA restored normal levels of UV resistance to XL216 cells. Microinjection of ERCC5 cDNA specifically restored the defect of xeroderma pigmentosum group G cells (XP-G) as measured by unscheduled DNA synthesis, and XP-G cells stably transformed with ERCC5 cDNA showed nearly normal UV resistance.

Amino Acid Sequence↗
PubMed1994

Purification and characterization of galactocerebrosidase from human lymphocytes.

Galactocerebrosidase was purified about 22,600-fold using several hydrophobic column and gel filtration steps with a 4.8% recovery, from human lymphocytes. Its specific activity was 1.54 x 10(5) nmol/h/mg with tritium-labeled galactocerebroside as the substrate in the taurocholate system. The optimal pH for galactocerebroside was 4.2 in the taurocholate system and 4.6 in the cholate system. The Km values for galactocerebroside were 5 microM in the taurocholate system and 25 microM in the cholate system. The molecular weight of the purified enzyme was estimated to be 90 kDa by sodium dodecylsulfate polyacrylamide gel electrophoresis and gel filtration. However, 70, 50, 40, and 30 kDa bands were also recognized on SDS-PAGE. The N-terminal amino acid sequences of the 70 kDa molecule and the three 50 kDa molecules were the same as that of the 90 kDa molecule. The N-terminal amino acid sequences of the 40 and 30 kDa molecules were unique. A monoclonal antibody raised against the purified enzyme effectively immunoprecipitated galactocerebrosidase activity, and an affinity column prepared with this monoclonal antibody bound the 90 and 50 kDa proteins. These results suggest that this enzyme is probably processed from the 90 kDa protein.

Amino Acid Sequence↗