Biomedical subjects
Publications and source records attributed to K Sano.
An electrophoretic method capable of analysing a small volume (5-10 microliter) of human palatine saliva without prior concentration was developed by combining the high resolution of isoelectric focusing in agarose with a highly sensitive silver protein staining method. Human palatine saliva exhibited 23 protein bands, those at pI 4.3-4.4, 4.7, 5.3 and 5.8 being major bands.
The effect of Nizofenone (Y-9179), a vertebral protective agent, on delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH) due to aneurysmal rupture was investigated by a cooperative double-blind clinical trials. Delayed ischemic neurological deficits following SAH are closely associated with the occurrence of vasospasm, and the effectiveness of any cerebral protective agent depends on sufficient coverage by the drug over the period around the onset of ischemic insult. Therefore, the study was designed so that the effect of Nizofenone could be analyzed in terms of these two factors. In patients admitted within day 9 of SAH, drug administration was immediately initiated and continued for 5 days. When delayed ischemic neurological deficits occurred, angiography was carried out to confirm the presence of vasospasm, and then drug administration was extended for an additional 5 days. Ten of the 100 cases enlisted in the study were excluded prior to code-breaking because of the occurrence of severe complications not related to vasospasm. Out of the 42 cases of the Nizofenone group and 48 of the placebo group, 25 and 29 developed vasospasm, respectively. Thus Nizofenone did not prevent vasospasm. Of the 25 cases of the Nizofenone group with vasospasm, 13 cases received sufficient drug coverage around the onset of vasospasm. The placebo group, the total Nizofenone group, and the Nizofenone group with sufficient drug coverage were stratified according to the occurrence of vasospasm. The disability status index one month after admission and the neurological functions, such as motor and speech functions, of each group were then compared. In patients who developed vasospasm, only the Nizofenone group with sufficient drug coverage had a significantly better outcome than the placebo group (p less than 0.05). No particular side effect of Nizofenone was observed. Thus, the results indicate that Nizofenone may be useful in the therapy of delayed ischemic neurological deficits following SAH, although the effect of the drug may be considerably influenced by the timing of its administration.
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Brain free fatty acids (FFAs) and brain water content were measured in gerbils subjected to transient, bilateral cerebral ischemia under brief halothane anesthesia (nontreated group) and pentobarbital anesthesia (treated group). Mortality in the two groups was also evaluated. In nontreated animals, both saturated and mono- and polyunsaturated FFAs increased approximately 12-fold in total at the end of a 30-min period of ischemia; during recirculation, the level of free arachidonic acid dropped rapidly, while other FFAs gradually decreased to their preischemic levels in 90 min. In treated animals, the levels of total FFAs were lower than the nontreated group during ischemia, but higher at 90 min of reflow, and the decrease in the rate of free arachidonic acid was slower in the early period of reflow. Water content increased progressively during ischemia and recirculation with no extravasation of serum protein, but the values were consistently lower in the treated group. None of the nontreated animals survived for 2 weeks; in contrast, survival was 37.5% in the treated group. It is suggested that barbiturate protection from transient cerebral ischemia may be mediated by the attenuation of both membrane phospholipid hydrolysis during ischemia and postischemic peroxidation of accumulated free arachidonic acid.
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In an effort to express the grades of mild disturbance of consciousness (MDOC), or clouding of consciousness, 25 items were selected for application in clinical examination. Factor analysis of the 25 items revealed that MDOC has a two-factor structure; namely, the performance factor (F1) and the verbal factor (F2). This structure was maintained in the sequential examinations. Guttman's scale analysis showed that the scale using the 25 items may be considered to approximate a unidimensional scale. By item selection according to communality, the 25 items could be reduced to 12 items without losing the two-factor structure or the usefulness and reliability of the examination. The principal component analysis (PCA) score, the F1 score, and the F2 score, calculated from the 12 items, were found to be good scales to describe an overall picture and characteristics of the F1 and the F2 of MDOC, respectively. Furthermore, by means of the characteristic curve (ogive) method, it was revealed that MDOC consisted of four clusters of items, the F2 factor (mild), F1 factor (mild), F2 factor (moderate), and F1 factor (moderate), according to the MDOC severity, so that a simpler scale composed of a representative item from each cluster could be constructed which exhibited a high correlation coefficient with the original PCA score.
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A single injection or 3 successive injections of nicotinamide (500 mg/kg body wt) increased NADPH-cytochrome c reductase and aniline hydroxylase activities of rat liver microsomes without changing cytochrome P-450 content. Oral administration of nicotinamide for 2 weeks resulted in significant increase in cytochrome P-450, indicating that nicotinamide was an inducer of cytochrome P-450 though its potency was weak. A kinetic study indicated that microsomes isolated from control rats contained only high affinity (low Km) form of aniline hydroxylase while microsomes isolated from nicotinamide-treated rats contained more high affinity form and a newly appeared-low affinity (high Km) form. These results suggest that there exist at least 2 different cytochrome P-450s participating in aniline hydroxylation in rat liver microsomes and nicotinamide induces the high Km form. Ethanol or nicotinamide consumption for 2 weeks resulted in enhancement of high affinity form and appearance of low affinity form but with slightly different Km values.
Two distinct dopamine binding sites, referred to as D1 and D2, exist in canine caudate nucleus, as characterized by [3H]dopamine binding to the synaptic membrane fraction. D1 has the low affinity for dopamine with the dissociation constant of a few micromolar, whereas the affinity for D2 is about two orders of magnitude greater. Classical neuroleptics such as haloperidol and chlorpromazine have no selectivity in the inhibition of D1 and D2 binding, whereas a number of 2-methoxy benzamide derivatives which have been synthesized in our laboratories exhibit rather different selectivity. Correlation between the selectivity of those benzamide derivatives for the two sites and the inhibition of apomorphine-induced stereotypy in rats suggests that D1 is more responsible for the stereotypy. Photoaffinity labeling of D1 and D2 with [3H]dopamine demonstrates that the two sites are distinct entities. In the D1 system, the adenylate cyclase which is responsive to Gpp(NH)p can be dissociable by the treatment with GTP-Sepharose into a guanine nucleotide binding unit and a catalytic unit which is insensitive to Gpp(NH)p. The catalytic unit restores the responsiveness to Gpp(NH)p after preincubation with the nucleotide binding unit. Furthermore, endogenous cAMP-dependent phosphorylation of two particular proteins (protein Ia and Ib) is shown, which may be at least partly responsible for stereotypy and dopamine turnover in the caudate nucleus.
In order to manipulate red cells to remove additives and metabolites prior to transfusion after prolonged preservation, osmotic fragility must be depressed. In isoosmotic sucrose solutions, the osmotic hemolysis curve is shifted to the left (less fragile) within several hours at 37 degrees C and within several days at 4 degrees C. However, hyperosmolar solution induced hemolysis when 0.9% NaCl was added after preservation. In isoosmotic sucrose solutions, the order of effectiveness in maintaining intracellular ATP content was: adenine plus inosine greater than inosine alone greater than adenine alone greater than no addition. The same order was also seen in depression of the increase in osmotic fragility during storage for 8 weeks. Formation of too stable erythrocytes to osmotic fragility and accordingly too low filtrability was prevented by the addition of appropriate amounts of physiological saline. Media containing isotonic sucrose, adenine and inosine depressed the increase in osmotic fragility during preservation for 6 weeks at 4 degrees C. ATP and 2,3-DPG levels were also better maintained than in various media containing a small amount of adenine. This finding with the former which indicated that the media containing isoosmotic sucrose, adenine and inosine prolonged posttransfusional viability of rabbit cells very much, suggests that these media are worthy of further investigation, since excess metabolites can be easily removed before transfusion.
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