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M Wachi

Publications and source records attributed to M Wachi.

65 records · Page 4Linked to original sources

Effects of methamphetamine administration on brain neurotensin-like immunoreactivity in rats.

The effects of methamphetamine (MAP) administration on neurotensin-like immunoreactivity (NTLI) were investigated in the rat brain. A single administration of MAP induced dose-dependent and reversible increases in NTLI in the caudate-putamen, limbic forebrain and midbrain. NTLI in the caudate-putamen, limbic forebrain and midbrain was also enhanced after repeated administration of MAP. It was assumed that MAP enhanced NTLI in the caudate-putamem, limbic forebrain and midbrain through its action upon the nigrostriatal and mesolimbic dopamine systems.

Animals↗

Clinical effects and plasma concentrations of long-term clonazepam monotherapy in previously untreated epileptics.

Ninety-three, previously untreated epileptics were subjected to clonazepam monotherapy. The plasma clonazepam concentrations were monitored to achieve optimal therapeutic effects of the drug. Within a mean duration of follow-up of 32 months, 57 (61.3%) of the 93 cases became seizure-free. The drug showed a high efficacy for complete seizure control of more than 80% for both simple partial seizures and primary generalized tonic clonic ones. The mean plasma level of clonazepam giving complete seizure control was 14.7 ng/ml (range: 3.0-34.6 ng/ml) in cases of generalized epilepsy, and 15.6 ng/ml (range: 4.5-42.3 ng/ml) in cases of partial epilepsy. There was a high correlation between the plasma level and the dose, but no correlation between the plasma level and the clinical effect of the drug. The variable therapeutic range and great interindividual differences in the optimal plasma clonazepam level imply that individually tailored regimens are necessary to achieve optimal therapeutic effects of the drug.

Adolescent↗

Mutant isolation and molecular cloning of mre genes, which determine cell shape, sensitivity to mecillinam, and amount of penicillin-binding proteins in Escherichia coli.

A chromosomal region of Escherichia coli contiguous to the fabE gene at 71 min on the chromosomal map contains multiple genes that are responsible for determination of the rod shape and sensitivity to the amidinopenicillin mecillinam. The so-called mre region was cloned and analyzed by complementation of two closely related but distinct E. coli mutants characterized, respectively, by the mutations mre-129 and mre-678, that showed a rounded to irregular cell shape and altered sensitivities to mecillinam; the mre-129 mutant was supersensitive to mecillinam at 30 degrees C, but the mre-678 mutant was resistant. The mre-678 mutation also caused simultaneous overproduction of penicillin-binding proteins 1Bs and 3. A chromosomal region of the wild-type DNA containing the total mre region and the fabE gene was first cloned on a lambda phage; a 7-kilobase (kb) fragment containing the whole mre region, but not the fabE gene, was then recloned on a mini F plasmid, pLG339; and finally, a 2.8-kb fragment complementing only mre-129 was also cloned on this low-copy-number plasmid. The whole 7-kb fragment was required for complementing the mre-678 mutant phenotypes. Fragments containing fabE but not the mre-129 region could be cloned on a high-copy-number plasmid. Southern blot hybridization indicated that the mre-678 mutant had a large deletion of 5.25 kb in its DNA, covering at least part of the mre-129 gene.

Amdinocillin↗

Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia coli chromosome.

The coding of two rare lipoproteins by two genes, rlpA and rlpB, located in the leuS-dacA region (15 min) on the Escherichia coli chromosome was demonstrated by expression of subcloned genes in a maxicell system. The formation of these two proteins was inhibited by globomycin, which is an inhibitor of the signal peptidase for the known lipoproteins of E. coli. In each case, this inhibition was accompanied by formation of a new protein, which showed a slightly lower mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which we suppose to be a prolipoprotein with an N-terminal signal peptide sequence similar to those of the bacterial major lipoproteins and lysis proteins of some bacteriocins. The incorporation of 3H-labeled palmitate and glycerol into the two lipoproteins was also observed. Sequencing of DNA showed that the two lipoprotein genes contained sequences that could code for signal peptide sequences of 17 amino acids (rlpA lipoprotein) and 18 amino acids (rlpB lipoprotein). The deduced sequences of the mature peptides consisted of 345 amino acids (Mr 35,614, rlpA lipoprotein) and 175 amino acids (Mr 19,445, rlpB lipoprotein), with an N-terminal cysteine to which thioglyceride and N-fatty acyl residues may be attached. These two lipoproteins may be important in duplication of the cells.

Amino Acid Sequence↗

Molecular cloning of the gene of a penicillin-binding protein supposed to cause high resistance to beta-lactam antibiotics in Staphylococcus aureus.

A novel penicillin-binding protein, PBP-2' (Mr about 75,000), is known to be induced in excessively large amount by most beta-lactam compounds in cells of a clinically isolated strain of Staphylococcus aureus, TK784, that is highly resistant to beta-lactams and also most other antibiotics. This protein has very low affinities to most beta-lactam compounds and has been supposed to be the cause of the resistance of the cells to beta-lactams. A 14-kilobase DNA fragment was isolated from the cells that carried the gene encoding this penicillin-binding protein and also a genetically linked marker that is responsible for the resistance to tobramycin. This DNA was cloned on plasmid pACYC184 and was shown to cause both production of PBP-2' and resistance to tobramycin in Escherichia coli cells. However, the formation of PBP-2' in E. coli was only moderate and was independent of normal inducer beta-lactams. The PBP-2' formed in the E. coli cells showed slow kinetics of binding to beta-lactams similar to that of PBP-2' formed in the original S. aureus cells and gave a similar pattern of peptides to the latter when digested with the proteolytic V8 enzyme of S. aureus.

Anti-Bacterial Agents↗

Effects of phencyclidine administration on behavior and brain neurotensin-like immunoreactivity in rats.

The effects of acute and chronic phencyclidine (PCP) administration on neurotensin-like immunoreactivity (NTLI) were investigated in discrete regions of rat brain. Both acute and chronic administration of PCP induced high locomotor activity, stereotypy and ataxia. On PCP administration, NTLI decreased significantly in the frontal cortex (Fc) alone. These results suggest that the decrease in NTLI in Fc is related to the behavioral abnormalities produced by PCP.

Animals↗

Absorption, distribution, metabolism and excretion of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)- 1,4-dihydropyridine (PP-1466) in rats.

In this experiment, the absorption, excretion, distribution and metabolism of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4-dihydropyridine (PP-1466) were investigated following oral or intravenous administration, single dose or repeated dose administration using male SLC-Wistar rats and the results of this investigation were summarized as follows: After oral administration of 14C-PP-1466 to rats, the blood level reached the maximum at 1 h and decreased with the biological half-life of about 5 h. The unchanged drug concentration in plasma was 30% of total concentration in plasma and disappeared at 6 h. The high radioactivities in the liver, kidney, fat, lung and adrenal gland were observed after oral and intravenous administration. After oral and intravenous administrations, the excretion in feces and urine during 48 h was 63.0 and 32.4, 58.6 and 41.6%, respectively. Biliary excretion amounted to 57.6 and 46.2% during 48 h, respectively. Six metabolites were found in the urine of rats. Three of them were identified as 2,6-dimethyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5-carboxylic acid pyridine, 2-methyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5-carboxylic acid-6-hydroxymethyl pyridine and its lactonizing analogue. These three metabolites covered 54% of total urinary metabolites. After oral repeated administration for three weeks, the excretion ratio of radioactivity in urine and feces was constant during the administration and no accumulation was observed in rat tissues.

Animals↗

Only oriC and its flanking region are recovered from the complex formed at the time of initiation of chromosome replication in Escherichia coli.

The oriC region of Escherichia coli constructs a specific complex to associate with the outer membrane fraction (oriC complex). The oriC complex was periodically formed before as well as in the short period after initiation of DNA replication. Using the DNA extracted from outer membrane fractions of the cells just after initiation as a probe, the whole E. coli genomic library was assayed by plaque hybridization. DNA regions that hybridized with the probe corresponded to about a 100-kb length of chromosome DNA which included oriC. In addition, clones located in a counterclockwise direction from oriC were more preferentially hybridized among these positive clones. Thus, we conclude that the oriC region is a unique locus of the chromosome that binds to the outer membrane at the time of initiation of chromosome replication.

Cell Membrane↗

Irregular nuclear localization and anucleate cell production in Escherichia coli induced by a Ca2+ chelator, EGTA.

A screening system for specific inhibitors of chromosome partitioning in Escherichia coli was constructed using the blue assay method developed for detection of anucleate cell production. Effects of known chemical compounds and antibiotics were examined in the system. It was found that a calcium-chelating reagent, EGTA, induced blue zones around the paper disks containing EGTA at concentrations which did not induce growth inhibition zones. Induction of anucleate cell production by EGTA was confirmed by fluorescence microscopy after DAPI staining. Even in the nucleated cells, irregular intracellular localization of nucleoids was frequently observed. The effect of EGTA was reversed by addition of Ca(2+). These results suggest the possible role of calcium ion in the process of chromosome partitioning in E. coli.

Anti-Bacterial Agents↗

Effects of ethanol administration on brain neurotensin-like immunoreactivity in rats.

The effects of acute and chronic ethanol administration on neurotensin-like immunoreactivity (NTLI) were investigated in discrete regions of the rat brain. Rats were administered a single dose (5 g/kg) of ethanol or rendered ethanol-dependent by repeated forced drinking of a 20% ethanol solution (6-15 g/kg) for 4 days and tested while still intoxicated or at 12-19 h (W-1) or 7 days (W-2) after ethanol withdrawal. Increases in NTLI were seen in the caudate-putamen in the toxic, W-1 and W-2 groups and decreases were observed in the midbrain in the toxic and W-1 groups. It was assumed that ethanol produced the changes of NTLI in the caudate-putamen and midbrain through its actions upon the dopaminergic system.

Alcohol Withdrawal Delirium↗