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Biomedical subjects

S Nakai

Publications and source records attributed to S Nakai.

At least 127 records · Page 7Linked to original sources

The effect of dose on the distribution of adriamycin encapsulated in polyethyleneglycol-coated liposomes.

The distribution of adriamycin (ADR) at a clinically relevant low dose of 2.5 mg/kg was compared to the distribution at a high dose of 7.5 mg/kg (dose often employed in distribution studies). ADR solution (ADRsol), plain liposomal ADR (PLADR) and polyethyleneglycol (PEG)-coated liposomal ADR (PEG-LADR) were injected into the tail vein of Wistar rats. The retention in serum was PEG-LADR > PLADR > ADRsol at both doses. In the high-dose study, ADR concentration in the liver and spleen at 4 h after administrations of PLADR and PEG-LADR were higher than that with ADRsol. On the other hand, in the low-dose study, reticuloendothelial system (RES) uptake of ADR was reduced by liposome encapsulation (liposomalization). Reduced ADR concentrations in the heart due to liposomalization were found only at the low doses. These results indicate that the difference in doses led to different distributions and that there is an optimal dose at which liposomes exhibit their objective distribution. A comparison of the ADR concentration in the spleen to that in the liver indicated RES saturation by increasing doses and the optimal dose being lower than the dose that saturates RES. Thus, distribution of liposome-entrapped ADR must be investigated at doses as close to the clinical dose as possible.

Animals↗

[Detection of numerical chromosomal aberrations by FISH in "DNA-diploid" head and neck squamous cell carcinomas].

We applied Fluorescence In Situ Hybridization to DNA-diploid head and neck squamous cell carcinomas to detect numerical chromosomal aberrations. Using centromeric repetitive probes of chromosomes 1, 7, 11, 17, X, and Y, we detected numerical aberrations of chromosomes in 4 of the 7 tumors examined, the main line of one tumor showed trisomy 1, while the other 3 tumors had subpopulations that showed trisomy or monosomy of 1 or 2 chromosomes examined. We found polyploidy by cytofluorometry in all 4 tumors with numerical chromosomal aberrations. These results suggest that from DNA-diploid tumors with polyploidy, subpopulation that are aneuploid at the chromosome level may arise before the ploidy of the main line shifts to over DNA-aneuploidy.

Carcinoma, Squamous Cell↗

Typical fibrolamellar hepatocellular carcinoma in Japanese patients: report of two cases.

We report herein the cases of two Japanese patients with typical fibrolamellar hepatocellular carcinoma treated at our institute. The first patient was a 19-year-old man with no hepatitis B or C viral infection and a normal, noncirrhotic liver in the nontumorous area. The second was a 36-year-old woman with no viral infection and a noncirrhotic liver in the nontumorous area. The clinicopathology, imaging appearances, and histology of both cases were similar to reports from the United States.

Adult↗

Effect of ageing on erythrocyte aldose reductase and sorbitol dehydrogenase activity.

We measured erythrocyte aldose reductase and sorbitol dehydrogenase activity in erythrocytes in healthy individuals aged from 16 to 91 years to determine the mechanism of age-dependent sorbitol accumulation. Erythrocyte aldose reductase activity increased significantly with age but ageing had no effect on sorbitol dehydrogenase activity. Age and the aldose reductase/sorbitol dehydrogenase ratio were positively correlated. These findings suggest that an increase in the ratio of aldose reductase to sorbitol dehydrogenase may contribute to the tissue accumulation of sorbitol in the elderly and may be a mechanism of a disease that is common in elderly individuals.

Adolescent↗

Effect of aging on plasma 1,5-anhydroglucitol levels in humans and rats.

Since normal reference values change with age in some clinical parameters, we measured the plasma levels of 1,5-anhydroglucitol (AG), a new marker of glycemic control in diabetes mellitus, in healthy subjects and in rats. Our results showed a significantly negative correlation of the marker with age in humans and that the plasma AG levels of older rats were markedly lower than those of younger counterparts. This remarkable reduction of AG in the older rat group can be partially explained by our finding that aged animals excreted AG more rapidly in the urine than younger ones, besides a decrease in food intake. We therefore suggest that normal clinical reference values for plasma AG levels should be modified according to age.

Adolescent↗

Combined treatment of autoimmune MRL/MP-lpr/lpr mice with a herbal medicine, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to) plus suboptimal dosage of prednisolone.

Therapeutic effects of combined treatment with a Chinese medicine prescription, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT) and suboptimal doses of prednisolone (PSL) on pathological findings of autoimmune-prone MRL/lpr mice were examined. Six-week-old MRL/lpr mice were treated orally with 1000 mg/kg of NYT, 0.5 or 2 mg/kg of PSL, 1000 mg/kg of NYT plus 0.5 or 2 mg/kg of PSL (combined treatment) or solvent only (control) six times per week. The rates of signs and symptoms of autoimmune disease (lymphadenopathy, proteinuria, dermatitis, loss of hair) were suppressed significantly in groups given PSL (2 mg/kg) alone, NYT alone and combined treatment with PSL (2 mg/kg) plus NYT (1000 mg/kg) compared with control, respectively, whereas treatment with PSL (0.5 mg/kg) alone did not inhibit their occurrence. ConA response and IL-2 production were also improved significantly in lymphocytes of mice given the combined treatment. Interestingly, treatment with NYT alone enhanced further the augmented IFN-gamma production in MRL/lpr mice but the combined treatment suppressed such an augmented production. The combined treatment dramatically reduced the level of anti-DNA antibodies in serum of MRL/lpr mice. By contrast, NYT alone treatment had no effect on autoantibodies production. These results suggest that combined treatment with NYT plus a suboptimal dose of PSL could be effective for systemic lupus erythematosus without severe side-effects.

Animals↗

Carbon monoxide and nitrogen dioxide exposures in indoor ice skating rinks.

Exposures to carbon monoxide (CO) and nitrogen dioxide (NO2) were determined in seven enclosed ice skating rinks and an outdoor rink. The uptake of CO was also determined by the difference in alveolar CO concentration of the non-smoking hockey players before and after games. Carbon monoxide concentrations in enclosed rinks ranged from 4 to 117 ppm and NO2 concentrations from 342 to 2729 ppb for 2 h hockey games. The CO uptakes were linearly related to the ambient CO concentrations. Alveolar CO of the hockey players increased on average by 0.53 ppm per 1 ppm CO exposure over 2 h. Considering the CO and NO2 levels currently measured in enclosed ice skating rinks, indoor air quality guidelines or standards should be established. It is recommended that 1 h maximum allowable limits of 20 ppm CO and 250 ppb NO2 be established.

Absorption↗

Systematic sequencing of the 180 kilobase region of the Bacillus subtilis chromosome containing the replication origin.

We have determined a 180 kb contiguous sequence in the replication origin region of the Bacillus subtilis chromosome. Open reading frames (ORF) in this region were unambiguously identified from the determined sequence, using criteria characteristic for the B. subtilis gene structure, i.e., starting with an ATG, GTG or TTG codon preceded by sequences complementary to the 3' end of the 16S rRNA. Four rRNA gene sets, 7 individual tRNA genes and 1 scRNA gene were identified, occupying 20 kb in total. In the remaining 160 kb region, 158 ORFs were identified, suggesting that 1 ORF is coded on average by 1 kb of DNA of the B. subtilis genome. Among the 158 ORFs, the functions of 48 ORFs were assigned and those of 11 ORFs are suggested through significant similarities to known proteins present in data banks. However, the functions of more than half of the ORFs (63%) remain to be determined.

Amino Acid Sequence↗

Preservation of high regional blood flow at epicardial rim after coronary occlusion in dogs.

A thin myocardial layer adjacent to the epicardium (epicardial rim) often survives after transmural myocardial infarction. Regional myocardial blood flow (Qm) at this rim may be high enough to maintain myocardial viability during coronary occlusion. To test this hypothesis, we measured Qm in 12 anesthetized dogs during left anterior descending coronary artery occlusion using nonradioactive colored microspheres. Myocardium in the region supplied by the occluded artery was sliced into sections approximately 0.5 mm thick from the epicardial surface to the endocardium, and the Qm in each section was determined. During occlusion, the Qm of myocardium within 0.5 mm of the epicardial surface remained at 74.8 +/- 8.8% of the preocclusion level. Maintenance of this high Qm during occlusion was abolished when an epicardial incision approximately 1 mm deep was made around the occluded area. These findings suggest that Qm is maintained at a surprisingly high level at the epicardial rim after coronary occlusion through epicardial arterial communications, which may be sufficient to maintain myocardial viability.

Animals↗

Determination of Kt/V and protein catabolic rate using pre- and postdialysis blood urea nitrogen concentrations.

We developed a new urea kinetic method for simultaneous determination of the Kt/V and protein catabolic rate (PCR) only from blood urea nitrogen (BUN) concentrations before and after a single dialysis session. Using this method, the parameters were calculated within 1.5 s even when a hand-held computer with a low central processing capacity is used. The total amount of urea eliminated during three dialysis sessions in 1 week is assumed to be equal to urea volume (Gw) generated over a 1-week period (Tw): [formula: see text]. Here, G is the generation rate, K is the dialyzer urea clearance, T is the dialysis time and C1, C2 and C3 are BUN during the respective dialysis session. If this equation and the equation expressing the urea kinetics during a single dialysis session are solved together, we have a solution for Kt/V and G. The thus-obtained Kt/V and G are corrected using the change in body weight. The corrected Kt/V showed a good correspondence with the parameter calculated with the classical method, and the midweek PCR derived from G determined by the present method being equivalent to the PCR averaged for a 1-week period determined by the classical methods.

Blood Urea Nitrogen↗