Shell effects on symmetric fragmentations of alkali-metal clusters.
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Biomedical subjects
Publications and source records attributed to A Tamura.
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Enantiomers of disopyramide (DP) and its mono-N-dealkylated metabolite (MND) were determined in human plasma and urine by enantioselective high-performance liquid chromatography using a chiral stationary-phase column. This method was precise and sensitive: the mean recoveries from plasma at a concentration of 0.5 microgram/ml were 101.1% for (+)-DP, 98.0% for (-)-DP, 94.4% for (+)-MND and 82.9% for (-)-MND; the within- and between-day coefficients of variation at the same concentration were 4.4 and 3.3% for (+)-DP, 4.7 and 4.1% for (-)-DP, 6.5 and 4.1% for (+)-MND and 7.8 and 2.4% for (-)-MND for plasma; the lower detection limits were 40 ng/ml for (+)-DP, 80 ng/ml for (-)-DP, 100 ng/ml for (-)-MND and 200 ng/ml for (+)-MND, for 0.5 ml of plasma and 0.2 ml of urine. The ultrafiltration technique was used for determination of the unbound concentration of DP enantiomers in plasma. A preliminary study of the determination of DP and MND enantiomers in plasma and urine samples from a healthy subject given racemic DP demonstrated the clinical applicability of the present method for therapeutic monitoring and pharmacokinetic studies.
A type-specific antigen (TSA) in Rickettsia tsutsugamushi is a 56-kDa protein located on the rickettsial surface. The gene (tsg56) encoding the TSA was isolated from R. tsutsugamushi Gilliam strain. Sequencing revealed an open reading frame of 1572 bp encoding a 524-amino acid (aa) protein with an Mr of 56,053. The deduced aa sequence consists of a 22-aa signal sequence and the mature TSA sequence (502 aa; Mr 53,803), whose N-terminal portion has the aa sequence determined directly in our previous study [Ohashi et al., Infect. Immun. 57 (1989) 1427-1431]. Alternate localization of hydrophobic and hydrophilic regions was recognized in the TSA molecule, suggesting that the TSA is a transmembrane protein. The codon usage in the A + T-rich (59%) tsg56 gene reflects a high A + T content of R. tsutsugamushi. The 5'-flanking region contains sequences similar to those of ribosome-binding sites and promoters of Escherichia coli.
Following brief cerebral ischemia, neurons are selectively damaged and die, whereas glial cells and blood vessels survive. This phenomenon of selective vulnerability is well illustrated in the hippocampal CA1 region. Five min of forebrain ischemia in the Mongolian gerbil produced selective neuronal necrosis in the hippocampal CA1 sector. After destruction and loss of CA1 neurons, a remarkable glial reaction (gliosis) was seen. The thickness of the CA1 subfield remained unchanged until 1 month after ischemia and then gradually shrank over several months. Ultrastructural observation of this region revealed persistent maintenance of presynaptic structures. Numerous presynaptic terminals containing synaptic vesicles were scattered throughout the gliotic scar tissue. These presynaptic terminals were apposed to degenerative structures which seemed most likely to be remnants of dendrites. In another group of animals, at one month following ischemic damage in the CA1 sector, the CA3 neurons were destroyed by kainic acid injection. In these animals, numerous degenerating presynaptic boutons were seen in the CA1 sector when fixed 4 days following kainate injection. These results indicate that even in gliotic tissue, presynaptic terminals can survive and maintain their structural characteristics although neuronal cell bodies are almost absent.
Following occlusion of the left middle cerebral artery in the rat, marked atrophy was observed in the ipsilateral substantia nigra in and after the second week. The mechanism of this neuropathological change in the substantia nigra, which is remote from the site of infarction, may be explained by transsynaptic, neurotransmitter-mediated disinhibition as a result of infarction of the striatum.
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A procedure which can detect subtype-specific minor bands of factor B (BF) by polyacrylamide gel isoelectric focusing is presented. After zymosan-mediated fragmentation of BF in serum via alternative pathway for complement activation, serum samples are subjected to isoelectric focusing in a narrow pH range (4.2-4.9). The Ba fragments are detected by using immunoblotting. In addition to the previously reported minor bands with subtypic specificities, heterogeneities are observed in other minor band group, where a single minor band corresponds exclusively to a subtype in a regular combination with the previously announced subtypic patterns. A one-to-one correspondence of a single band to each subtype provides an unambiguous determination for three subtypic phenotypes deduced from the two divided BF*F alleles, BF*FA and BF*FB. An autosomal codominant heredity is confirmed through segregation analysis. A population survey reveals that four common alleles, BF*S, BF*FA, BF*FB, BF*Fb1, occur in a Japanese population and the former three alleles, except BF*Fb1, occur in a Cambodian population. The presence or absence of a single anodal minor band was found to be the only difference after neuraminidase treatment of FA and FB, implying that an amino acid substitution responsible for the FA-FB subtypic difference is involved in an additional acquisition in FA of an oligosaccharide unit with a charged sialic acid.
A 47 year old woman who underwent surgical section of the posterior half of the corpus callosum because of meningioma in the right lateral ventricle was studied from the aspects of speech perception and auditory evoked potentials. The pure tone audiometry showed normal hearing levels for both ears. The monosyllable perception test disclosed that the left ear had lower correct percent than the right ear. The dichotic listening test demonstrated remarkable extinction in response to verbal stimuli in the left ear. Auditory brainstem, middle latency and slow vertex responses were normal for both ears, without right and left difference. P300 event related potentials were recorded by three different pairs of stimuli: pure tone (1 KHz vs. 2 KHz), words (Aka vs. Kuro), and monosyllable (PA vs. BA). Both P300 for pure tone and word stimuli to each ear showed large positive potentials within 200-500 msec but P300 for monosyllable stimuli to each ear did not show obvious potentials within 200-500 msec. These results suggest that the posterior half of the truncus of the corpus callosum can be related to transfer of speech information between right and left hemispheres.
1. Focal cerebral ischemia was induced in anesthetized rats by occluding the stem of the proximal middle cerebral artery. 2. The levels of free fatty acids, such as stearic and arachidonic acids, in the ischemic cerebral cortex increased progressively until 60 min after occlusion, but thereafter they decreased rapidly. 3. In contrast to the time-dependent changes in free fatty acids, the levels of triacylglycerol (TAG) in the ischemic cerebral cortex continued to increase for 120 min after occlusion. Increases in TAG-palmitate, -stearate and -arachidonate accounted for the increase in the triacylglycerol level. 4. The pattern of the lipid changes in focal cerebral ischemia differs from those reported in bilateral diffuse cerebral ischemia induced by arterial occlusion or in decapitation ischemia.
We investigated the possibility that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed or even regressed when their serum cholesterol levels were kept extremely low. Ten-month-old WHHL rabbits were divided into 3 groups, i.e. control rabbits, sacrificed at age 10 months, and placebo and treated rabbits, sacrificed at age 18 months. The treated rabbits were given pravastatin sodium (50 mg/kg/day), an HMG-CoA reductase inhibitor, in combination with cholestyramine (2% in diet), a bile acid sequestrant, for 36 weeks. The serum cholesterol levels and atherogenic lipoproteins in the treated group were markedly reduced, by about 60% (P less than 0.005 and P less than 0.001). Consequently, the degrees of both coronary and aortic atherosclerosis in the treated group were significantly reduced compared with the placebo group, and were almost the same as in the control group. The histopathological findings supported the above results. In addition, the incidence and degree of xanthomas in digital joints in the treated group were significantly reduced. These results suggest that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed by keeping their serum cholesterol levels extremely low by the combination drug treatment.
To clarify the involvement of neurotransmitters in the remote metabolic effect following focal ischaemia, amino acid neurotransmitter candidates--GABA, aspartate and glutamate--were measured time-sequentially in the basal ganglia following middle cerebral artery occlusion in the rat, which is known to produce a change in glucose metabolism and blood flow in the remote basal ganglia. GABA and aspartate content decreased in the ipsilateral substantia nigra from the second to the 28 th postoperative day. The same tendency was observed in the ipsilateral globus pallidus. Glutamate did not change significantly in either nucleus. In the contralateral side, GABA increased significantly in the substantia nigra throughout the experimental period and in the striatum during the first seven days. These results indicate that the destruction of strionigral tract by focal ischaemia induced the decrease of inhibitory GABA in the ipsilateral substantia nigra. The increase of metabolism in this nucleus may be caused by the decrease of the inhibitory effect.
Factors which influence the plasma drug concentrations in whole blood have been investigated in-vitro using human blood containing radio-labelled phenytoin or chlorpromazine. Phenytoin (3.55 micrograms mL-1, 0.01 mM) or chlorpromazine (2.74 micrograms mL-1, 0.01 mM) was mixed with normal or modified blood and the plasma drug level was measured. Plasma phenytoin and chlorpromazine levels decreased with decrease in the protein concentration of plasma, but were not influenced by addition of gamma-globulin to the blood specimen. Plasma phenytoin levels increased with an increase in haematocrit from 20 to 45%, whereas the chlorpromazine level remained constant. The partition coefficients of phenytoin and chlorpromazine between blood cells and plasma were almost the same at various haematocrit values. By cooling the blood containing each drug to 4 degrees C, plasma phenytoin and chlorpromazine levels were higher compared with those at 37 degrees C. Similar temperature effects on the drug levels in plasma were obtained when the washed erythrocytes were resuspended in albumin medium, but not when resuspended in saline.
Microimmunofluorescence (IF) and immunoperoxidase tests are generally used for the serodiagnosis of scrub typhus. While these tests give satisfactory results in the hands of experienced personnel, they can be troublesome for inexperienced technicians. To develop a simpler diagnostic method, dot-blot assay was examined in this study. Six antigenically distinctive strains of Gilliam, Karp, Kato, Shimokoshi, Kawasaki and Kuroki of Rickettsia tsutsugamushi and a strain of Rickettsia sibirica were dotted on a nitrocellulose sheet by a dot-blot instrument. The sheets were treated with patient sera, followed by peroxidase-conjugated anti-human immunoglobulin-antibody and then with the substrate of the enzyme, and the color development on the dots was compared by naked eye observation. By this procedure, anti-rickettsial antibody-positive patient sera showed clear color development on at least one, usually several dots, while the very faint color was observed by the treatment with antibody-negative sera. On the other hand, it was ascertained that the antigens on nitrocellulose sheets were stable for at least 4 months at room temperature. Therefore the diagnostic kits were prepared, and the practical application of this procedure for diagnosis of scrub typhus were tested in Shizuoka and Miyazaki Prefectural Pabulic Health Laboratories. The results indicated a very good comparability between the dot-blot assay and IF-tests, and this dot-blot method was ascertained as a simple and useful method for the scrub typhus serodiagnosis.
The Kuroki strain of Rickettsia tsutsugamushi, isolated from a patient in Kyushu, Japan, has a major, type-specific antigenic polypeptide which is distinct from the prototype strains in size (58 kilodaltons), in antigenicity, and in its cleavage pattern with N-chlorosuccinimide. These results indicate that Kuroki is another antigenic type of R. tsutsugamushi.
Permanent middle cerebral artery occlusion in rats results in infarction in the ipsilateral cortex and caudate nucleus-putamen. In this ischemia model, severe shrinkage of the ipsilateral half of the thalamus was observed several months after surgery. We examined the serial profile of this phenomenon in 40 rats at intervals from 2 weeks to 6 months after the operation. The area of the ipsilateral half of the thalamus as a percentage of the area of the contralateral half was 87% at 2 weeks, 77% at 1 month, 54% at 3 months, and 54% at 6 months. Such severe morphologic change distant from the original ischemic focus has not been reported in models of experimental focal ischemia. Retrograde degeneration is thought to play an important role in this phenomenon.
Using an immunoblotting technique, we investigated changes in the concentrations of microtubule-associated protein 2, 200-kDa neurofilament, tubulin, myelin-associated glycoprotein, and 2':3'-cyclic nucleotide 3'-phosphodiesterase in the brains of 40 rats following occlusion of the left middle cerebral artery or sham operation. Compared with those 4 hours after surgery, concentrations of all proteins decreased significantly in the left hemisphere 3 days after surgery (p less than 0.01). Microtubule-associated protein 2 was the most susceptible to ischemia, and its mean +/- SEM concentration decreased to 23 +/- 9.4% of that in concurrent sham-operated controls. Degradation products of microtubule-associated protein 2 and myelin-associated glycoprotein were detected on the blots. Furthermore, in the contralateral hemisphere (where calpain might be activated), concentrations of these two proteins decreased to 57 +/- 12.0% and 83 +/- 4.3% of those in concurrent sham-operated controls, respectively, 3 days after surgery. Changes in the concentrations of cerebral proteins in the contralateral hemisphere are important for understanding clinical symptoms not attributable solely to the ipsilateral lesion following a focal cerebral stroke.
An antioxidant activity of indapamide (IDP) and its metabolite (OH-IDP) is demonstrated in this study. Both IDP and OH-IDP were found to scavenge 1,1-diphenyl-2-picryl-hydrazyl free radical. The scavenging effect of OH-IDP was stronger than that of IDP. Lipid peroxidation of rat liver microsomes initiated by reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine diphosphate (ADP)-Fe3+ was inhibited by IDP and OH-IDP with IC50 values of about 6 and 2 microM, respectively. The lipid peroxidation in human erythrocyte membrane, induced by 2,2'-azobis-(2-amidinopropane dihydrochloride) treatment, was also inhibited by 10 microM IDP. The antioxidant capacity of OH-IDP was at almost the same level as that of alpha-tocopherol, tested for comparison. The present data show that IDP and OH-IDP at micromolar concentrations are able to trap the free radicals involved in the lipid peroxidation.
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