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Biomedical subjects

Y Onodera

Publications and source records attributed to Y Onodera.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dual inhibitory activity of sitafloxacin (DU-6859a) against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae.

The in-vitro inhibitory activities of sitafloxacin (DU-6859a) and other quinolones against Streptococcus pneumoniae DNA gyrase and topoisomerase IV were measured. IC50s of levofloxacin, ciprofloxacin, sparfloxacin and tosufloxacin against DNA gyrase were almost three to 12 times higher than those against topoisomerase IV. On the other hand, sitafloxacin showed dual inhibitory activity against both enzymes and its IC50s were the lowest among those of the quinolones tested. These results suggest that sitafloxacin is an effective agent against pneumococcal infections and that the incidence of drug-resistant mutants is low.

Anti-Infective Agents↗
PubMed1999

Molecular cloning of the gyrA and gyrB genes of Bacteroides fragilis encoding DNA gyrase.

The genes encoding the DNA gyrase A and B subunits of Bacteroides fragilis were cloned and sequenced. The gyrA and gyrB genes code for proteins of 845 and 653 amino acids, respectively. These proteins were expressed in Escherichia coli, and the combination of GyrA and GyrB exhibited ATP-dependent supercoiling activity. To analyze the role of DNA gyrase in quinolone resistance of B. fragilis, we isolated mutant strains by stepwise selection for resistance to increasing concentrations of levofloxacin. We analyzed the resistant mutants and showed that Ser-82 of GyrA, equivalent to resistance hot spot Ser-83 of GyrA in E. coli, was in each case replaced with Phe. These results suggest that DNA gyrase is an important target for quinolones in B. fragilis.

Amino Acid Sequence↗
PubMed1999

Cloning, expression, and enzymatic characterization of Pseudomonas aeruginosa topoisomerase IV.

The topoisomerase IV subunit A gene, parC homolog, has been cloned and sequenced from Pseudomonas aeruginosa PAO1, with cDNA encoding the N-terminal region of Escherichia coli parC used as a probe. The homolog and its upstream gene were presumed to be parC and parE through sequence homology with the parC and parE genes of other organisms. The deduced amino acid sequence of ParC and ParE showed 33 and 32% identity with that of the P. aeruginosa DNA gyrase subunits, GyrA and GyrB, respectively, and 69 and 75% identity with that of E. coli ParC and ParE, respectively. The putative ParC and ParE proteins were overexpressed and separately purified by use of a fusion system with a maltose-binding protein, and their enzymatic properties were examined. The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. So, the cloned genes were identified as P. aeruginosa topoisomerase IV genes. The inhibitory effects of quinolones on the activities of topoisomerase IV and DNA gyrase were compared. The 50% inhibitory concentrations of quinolones for the decatenation activity of topoisomerase IV were from five to eight times higher than those for the supercoiling activities of P. aeruginosa DNA gyrase. These results confirmed that topoisomerase IV is less sensitive to fluoroquinolones than is DNA gyrase and may be a secondary target of new quinolones in wild-type P. aeruginosa.

4-Quinolones↗
PubMed1999

Analysis of liver single photon emission computed tomography in a case of fulminant hepatic failure.

Fulminant hepatic failure is associated with a high mortality rate. Thus, accurate assessment of hepatic functional reserve and hepatic regeneration is important. We describe a 67-year-old woman who survived subacute hepatic failure. We had an opportunity to monitor the clinical course of the patient using single photon emission computed tomography (SPECT) with 99mTc-galactosyl-human serum albumin (99mTc-GSA) and frequent hematological examinations. On admission, prothrombin time was remarkably prolonged (23.1% of control). The liver uptake of 99mTc-GSA was also considerably low. She responded well to treatment. Four weeks after admission, SPECT analysis showed a dramatic increase in liver uptake of 99mTc-GSA, suggesting promotion of hepatic regeneration. Moreover, functional liver volume calculated from the SPECT data showed a marked increase at 4 weeks after admission, whereas CT scan showed no change at that point. This indicated that SPECT with 99mTc-GSA reflected functional hepatocytes more accurately than liver volume determined by CT scan, which cannot exclude nonfunctional hepatocytes. The patient's condition improved in parallel with the improvements in the indices measured by SPECT and hematological examinations. SPECT analysis is practically useful for the prompt assessment of improvement in patients with fulminant hepatic failure.

Aged↗
PubMed1999

Therapeutic efficacy of transcranial magnetic stimulation for hereditary spinocerebellar degeneration.

We applied transcranial magnetic stimulation (TMS) as a therapeutic approach for patients with spinocerebellar degeneration (SCD). The subjects were four familial SCD patients (three men and one woman) aged from 27 to 76 years old. They were genetically analysed as two spinocerebellar ataxia type 6 (SCA 6), one SCA 1, and one SCA 7. The durations of their illness ranged from 1 to 7 years. Ten consecutive magnetic pulses were delivered over the scalp corresponding to the right cerebellar hemisphere, the middle of the cerebellum and the left cerebellar hemisphere, respectively, every day for 21 days. In all patients, the time and the number of steps required for a 10 m walk examination were significantly decreased after TMS trial compared with those before TMS. The number of feasible steps in tandem gait test increased. The total length of tracing body balance for 30 seconds measured by gravinometer was significantly decreased. However, nystagmus, dysarthria or incoordination of the upper limbs did not change after TMS trial. It is of interest that the blood flow of the cerebellar hemisphere, putamen and pons were significantly increased during the TMS trial. Although we do not know the exact mechanism by which TMS improved the ataxic gait, we speculate the increase of blood flow in the cerebellum, putamen and pons takes part in the improvement. These findings suggest that TMS over the cerebellum may be an effective therapy for patients with SCD.

Adult↗
PubMed1999

[Evaluation of the liver uptake rate measured by 99mTc-GSA SPECT to assess liver function].

Whether the global liver uptake rate of 99mTc-GSA directly measured by SPECT is useful as a new index of liver function was evaluated in comparison with biochemical test results (PT%, ChE, Alb, ICG R15, KICG) and Child classification. 99mTc-GSA SPECT was performed in 157 patients with diffuse hepatic disease or hepatobiliary tumor, and two indices, namely the global liver uptake rate measured by SPECT 15 minutes after intravenous injection of 99mTc-GSA (LUS 15) and liver uptake per volume (liver uptake density) were examined. Both LUS 15 and liver uptake density were significantly correlated with biochemical test results and Child classification. In particular, close relationships between LUS 15 and ICGR15 (r = -0.720, p < 0.0001), LUS 15 and KICG (r = -0.750, p < 0.0001), and between LUS 15 and ChE (r = 0.720, p < 0.0001), indicate that LUS 15 is a useful index to evaluate liver function. Moreover, the local liver uptake rate measured by SPECT represented regional liver function and was considered a useful index to predict the function of the remnant liver after invasive treatment such as surgery.

Adult↗
PubMed1998

Cytoplasmic diversity in leaf beet cultivars as revealed by mitochondrial DNA analysis.

Mitochondrial (mt) DNA restriction fragment length polymorphisms are convenient markers for identifying cytoplasmic variation among plant cultivars. In an attempt to detect new cytoplasmic genotypes useful for sugarbeet breeding, we have compared the hybridization patterns of mtDNA from three groups of cultivated beets, viz. leaf beet, garden beet, and fodder beet. Utilized as probes were the two sugarbeet mtDNA clones that were capable of distinguishing normal fertile and different sources of male-sterile cytoplasms from one another. The analysis allowed the identification of four chondriome types among 14 leaf beet cultivars examined. Two out of the four chondriome types were found to be different from the previously described fertile or male-sterile chondriome type. Our results thus indicate that leaf beet cultivars and landraces make up the primary cytoplasmic gene pool of the sugarbeet.

Base Sequence↗
PubMed1998

Quinolone resistance mutations in the GrlB protein of Staphylococcus aureus.

Two altered GrlB proteins (one with an Asp-432-->Asn alteration and one with an Asn-470-->Asp alteration) of Staphylococcus aureus were purified as fusion proteins to maltose-binding protein. The 50% inhibitory concentrations of levofloxacin were 14 and 3.4 microg/ml against topoisomerase IV containing GrlB proteins with alterations at positions 432 and 470, respectively. These results suggest that the alteration of Asp to Asn at position 432 may be responsible for quinolone resistance.

Anti-Infective Agents↗
PubMed1997

Inhibitory activities of quinolones against DNA gyrase and topoisomerase IV purified from Staphylococcus aureus.

In order to clarify the mechanism of action of quinolones against Staphylococcus aureus, GrlA and GrlB proteins of topoisomerase IV encoded by genes with or without mutations were purified separately as fusion proteins with maltose-binding protein in Escherichia coli. The reconstituted enzymes showed ATP-dependent decatenation and relaxing activities but had no supercoiling activity. The inhibitory effects of quinolones on the decatenation activity of topoisomerase IV were determined by quantitative electrophoresis with kinetoplast DNA as a substrate. The 50% inhibitory concentrations (IC50s) of levofloxacin, DR-3354, DU-6859a, DV-7751a, ciprofloxacin, sparfloxacin, and tosufloxacin against topoisomerase IV of S. aureus FDA 209-P were 2.3, 97, 0.45, 1.5, 2.5, 7.4, and 1.8 microg/ml, respectively, and were correlated well with their MICs. The IC50s of these drugs were from 2 to 20 times lower than those for the DNA gyrase. These results support genetic evidence that the primary target of new quinolones is topoisomerase IV in quinolone-susceptible strains of S. aureus. Three altered proteins of topoisomerase IV containing Ser-->Phe changes at codon 80 or Glu-->Lys changes at codon 84 of grlA, or both, were also purified. The inhibitory activities of quinolones against the topoisomerase IV which contained a single amino acid change were from 8 to 95 times weaker than those against the nonaltered enzyme. These results suggest that the mutations in the corresponding genes confer quinolone resistance.

DNA Topoisomerase IV↗
PubMed1997

[Functional MRI using interleaved EPI].

One of main purposes of functional MRI is to identify functional map on human brain. We considered spatial resolution was a important factor and investigated influences of it on signal changes and activated region size. Functional images were acquired with Echo-Planar imaging (EPI) and interleaved EPI (IEPI). IEPI is superior in spatial resolution but inferior in signal to noise ratio (SNR) to EPI. As a result of Student's t-test analysis, activated region sizes of IEPI reduced to less than half those of EPI while IEPI had larger signal increase than EPI. We confirmed that the reduction was caused by low SNR and our estimation analysis could prevent it.

Brain↗
PubMed1997

[Somatotopical mapping of the human somatosensory cortex with echo-planar MRI].

The somatotopical organization of the somatosensory cortex was analyzed. Echo-planar imaging was used to obtain functional images, and magnetic field strength was 1.5T. Natural stimulation at a frequency of 3 Hz (scrubbing or tapping) was applied to one of the three cutaneous areas: toes, fingertips, and tongue tip. The focal bands which show the significant signal increases were located on the contralateral post-central gyrus, and these changes of signal intensity originate from the cortical parenchyma because there were no major veins in the central sulcus. The focal bands which respond to each stimulation sites were anatomically distinct and located medially-to-laterally in the order of toes, fingertips, and tongue tip.

Adult↗
PubMed1997

Two types of micturitions of ileal neobladder.

Eight patients were evaluated clinically, radiologically, and urodynamically to determine the outcome of continent urinary diversion with ileal neobladder performed to treat the recurrent superficial bladder cancer after cystectomy with subcapsular prostatectomy. The mean age of the patients was 55.3 years. After descending dissection of the urinary bladder without ligation or dissection of Santorini's plexus, the prostate was cut to the bladder neck distally for 2 cm under the subcapular prostatectomy. One patient who had a short 3 cm intestinal segment between the pouch and the urethra, had severely prolonged micturition with peristalsis in this short segment, and required a re-operation. Micturition was good in the other seven patients, all with detubularized neobladder directly to the prostate capsule in anastomosis. Pressure flow studies performed on these seven patients revealed two types of micturition; "fast bladder" and "intermittent flow", the latter resembling detrusor sphincter dyssynergia.

Electromyography↗
PubMed1996

A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan.

We have identified a novel two-base mutation in exon 1 of the Cu/Zn superoxide dismutase (SOD1) gene (TGC to TTT), which resulted in Cys6 to Phe substitution in a Japanese family with amyotrophic lateral sclerosis (ALS). This is the first case of familial ALS-associated two-base change of the SOD1 gene. Similar to several mutations in exon 1 of the SOD1 gene such as Ala4 to Val, Ala4 to Thr and Val14 to Met, affected members of the present family showed a rapid progression of motor dysfunction. Although Ala4, Cys6 and Val7 reside in the middle of the first beta-strand of the SOD1, a family with a mutation of Val7 to Glu associates with slow progression of the disease. These findings suggest that clinical courses are variable with each mutation, even in the same exon.

Amino Acid Sequence↗
PubMed1996

[Contamination levels to room air arising from the use of 99mTc-gas and prevention from the contamination].

99mTc-gas (TECHNEGAS) is a 99mTc-labeled micro-aerosol which is considered to have different behavior from 133Xe or 81mKr gas. In order to estimate contamination levels to room air arising from the use of 99mTc-gas, filtered expired air during administration and 1, 2, 3, 5, 10 min after the administration were collected in each polyethylene bag. Radioactivities of the polyethylene bags, used filter and the lung were measured with 3-head scintillation camera. The activity of the expired air diminished within 6-10 min and about 5% of whole discharged 99mTc-gas was released to room air. The activity of the used filter was two times of the lung. According to these results, it is recommended that the 99mTc-gas may be administrated in a exclusive room. The administrated patient and used filter must be remain in the exclusive room.

Aerosols↗
PubMed1995

Functional mapping of the human colour centre with echo-planar magnetic resonance imaging.

Clinical studies of cerebral achromatopsia have suggested a colour centre in the human fusiform gyrus. By using functional magnetic resonance imaging, we examined whether the fusiform gyrus shows activity correlated with the perception of colour. We tested three stimulus conditions in which the subject maintained fixation: (i) a circular array of six coloured circles; (ii) the same as (i) except that each circle is equiluminant grey with its colour counterpart; and (iii) the same as (i) plus a clockwise shift of circles to neighbouring positions every 1 s. After termination of the stimulus, the subject perceived an after-image of circles with complementary colours in (i), but not in (iii). In condition (i), we found a focal signal increase in the posterior part of the fusiform gyrus. In condition (ii), the activation in the same locus during the stimulation period was weaker than that in (i). In condition (iii), the signal intensity after termination of the stimulus was weaker than that in (i). The colour effect and after-effect on activation of the fusiform gyrus observed here suggest its critical role in human colour perception.

Brain Mapping↗
PubMed1995

Functional mapping of the human somatosensory cortex with echo-planar MRI.

The somatotopical organization of the human somatosensory cortex was analyzed with echo-planar imaging at 1.5 Tesla, utilizing deoxyhemoglobin as an endogenous contrast medium. Scrubbing stimulation at a frequency of 3 Hz was applied to one of three cutaneous areas: toes, fingertips, and tongue tip. Parasagittal echo-planar slices were obtained every 2 s. We found focal bands of increased signal intensity (4% on average) during the stimulation, with a rise time of 2-6 s. These activated bands were located on the contralateral postcentral gyrus. The cortical responses from the three stimulation sites were anatomically distinct and organized medially-to-laterally in the order of toes, fingertips, and tongue tip.

Adult↗