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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 811 records · Page 45Linked to original sources

Tick bite: two cases studied by scanning electron microscopy.

The attachment of ticks to human skin has been studied by scanning electron microscopy. Intact specimens of Ixodes ovatus and Ixodes persulcatus were examined, and we also studied the skin of two patients who had been bitten by these two species. In the first case, the remains of the tick were visible and a homogeneous cement-like substance was observed on the dorsal hypostome and in the dermis, suggesting that the tick attaches itself to the host skin by a secretion. In the second case, the apices of some denticles of the hypostome were chipped. Two months later, the skin which the tick had attacked was biopsied and yellowish-brown particles, probably derived from the denticles, were seen in foreign body giant cells in the dermis.

Adolescent↗

Two new opioid delta-receptor ligands: a highly selective agonist and a potent selective antagonist in in vitro isolated preparations.

N,N-Diallyl derivatives of enkephalin analogues were chemically synthesized, and their biological activities were estimated in vitro isolated preparations. N,N-Diallyl-[D-Ala2, D-Leu5]-enkephalin [test compound I] at doses up to 10 microM did not inhibit the electrically-evoked contractions of guinea-pig ileum, which had been suggested to contain opioid mu- and kappa-receptors, but it significantly depressed the contractions of mouse vas deferens, which had been indicated to contain mu-, kappa- and delta-receptors, suggesting that test compound I did not act on both mu- and kappa-receptors, but acted on delta-receptors. Additionally, the Ke (equilibrium dissociation constant) values against test compound I of naloxone were approximately 30 nM and similar to those of Mr 2266, also indicating that test compound I acted as a delta agonist. Moreover, the Ke values of ICI 154129 against compound I were approximately 340 nM, strongly suggesting that test compound I acted as a delta agonist. The Ke values of bis-[N,N-diallyl-[D-Ala2, Leu5]-enkephalyl]-cystine [test compound II] against [D-Ala2, D-Leu5]-enkephalin in mouse vas deferens and morphine or ethylketocyclazocine in guinea-pig ileum were 44.9 nM and 5.00 or 11.3 microM, respectively, showing that test compound II was a potent selective opioid delta antagonist. In conclusion, among compounds synthesized, two new opioid delta-receptor ligands, one being a highly selective agonist and the other being a potent selective antagonist in in vitro isolated preparations, were found in the present study.

Animals↗

The role of bestatin-sensitive aminopeptidase, angiotensin converting enzyme and thiorphan-sensitive "enkephalinase" in the potency of enkephalins in the guinea-pig ileum.

The role of each enkephalin-hydrolyzing peptidase in the inhibitory potency of exogenously added enkephalins in the myenteric plexus-longitudinal muscle preparation of guinea-pig ileum was studied by using the relatively specific inhibitor of each enzyme. Results showed that three distinct enzymes, bestatin-sensitive aminopeptidase(s), angiotensin converting enzyme, and thiorphan-sensitive "enkephalinase", played a critical role in the inactivation of enkephalins. Additionally, these enzymes are likely to be located close to opioid receptors, since they produce a significant concentration difference of enkephalin between the surrounding organ bath and the vicinity of opioid receptors. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase are indicated not to be involved significantly in the degradation of exogenously added enkephalins in the guinea-pig ileum.

Amino Acids, Sulfur↗

Effects of metal-containing drugs taken simultaneously with clioquinol upon clinical features of SMON.

In order to explore the effects of metals upon the subsequent onset of several clinical events in SMON, a retrospective cohort study was attempted. Study subjects were 216 "exposed" patients and 149 "unexposed" patients. "Exposure" was defined as the simultaneous ingestion of metal-containing drugs with clioquinol before the onset of neurological disorders. These two cohorts were identified from 531 patients among 832 patients, collected by the nationwide survey in 1975 and 1976. Effects provoked by ingestion of five metals (alminum, calcium, magnesium, copper and bismuth) were evaluated by relative risks with and without adjustment of the total amount of clioquinol ingested. Adjusted relative risks were estimated by maximum likelihood method. Significance of relative risk was determined by its 95% confidence interval. Following major findings emerged from the present analysis. (1) Simultaneous ingestion of Al-, Ca-, Mg-, Cu- or Bi-containing drugs with clioquinol significantly reduced the risk of developing motor disturbances. (2) Risk of developing visual disturbances were favorably modified by Al-containing drugs. (3) Clinical severity was significantly reduced by ingestion of Al-, Ca-, Mg- or Bi-containing drugs. (4) About 2-fold increase in risk of unfavorable clinical course was demonstrated by Al-containing drugs. (5) Onset of both green-fur on the tongue and relapse appeared unrelated to the metal-containing drugs ingested. (6) Combined ingestion of two kinds of metal-containing drugs with clioquinol appeared to yield more favorable effects than single ingestion of metal-containing drugs. (7) Al- or Bi-containing drugs demonstrated the strongest association with clinical features of SMON, followed by the drugs containing Mg or Ca. Cu-containing drugs had little association.

Clioquinol↗

Factors influencing methylazoxymethanol acetate initiation of liver tumors in Oryzias latipes: carcinogen dosage and time of exposure.

Hepatic tumors were produced in the medaka (Oryzias latipes) kept at 25 degrees C in aquaria after exposure to methyl azoxymethanol (MAM) acetate. The tumors, including trabecular carcinomas and cholangiomas, were observable after 2-3 months. A similar incidence, i.e., nearly 100%, was found after a long-time exposure to a low level (0.1 ppm for 120 days) and after a short exposure to a high level (10 ppm for 1 hr) of MAM acetate. The relationship between the level of MAM acetate (0-2.0 ppm) and tumor incidence was studied after exposure for 1 day. The incidence increased as the level of drug increased, although an apparent threshold was seen at low levels. The incorporation of [3H]thymidine into the liver greatly increased over the period of 6-20 days after treatment with 0.5 ppm for 3 days. However, only a slight increase in incorporation was found when fish were treated continuously with a low level (0.1 ppm) from days 30 through 90. No reduction of tumor incidence was found when the carcinogen was given in 2 divided doses separated by various intervals, compared with a single exposure.

Animals↗

Prediction of male lung cancer mortality in Japan based on birth cohort analysis.

The future trend in male lung cancer mortality in Japan was predicted by using a simulation model. The model was based on the age-specific death rates from lung cancer in males by birth cohort, expressed as Fi(t) = rkSitr-1 exp(-ktr). The parameters in the function were obtained from the mortality data in Vital Statistics (1960-1980). The chi-square test for goodness-of-fit supported the statistical validity and acceptability of the function. Extrapolation of the function provided future age-specific death rates by birth cohort for males in Japan. In this simulation model it was possible to evaluate the effects of preventive strategies and/or therapeutic improvements on lung cancer mortality when five additional parameters were taken into consideration. According to this model, the age-adjusted death rate from lung cancer in Japanese males is predicted to increase linearly until the year 2000 and to level off thereafter. The total number of deaths from lung cancer for all Japanese males is predicted to be 27,000 in 1990 and over 40,000 in 2000. With the establishment of an effective preventive strategy for young generations, the mortality would begin to decrease a few decades later. Improvements in the therapy of lung cancer, if realized, might suppress the future upward mortality trend in Japan to some extent. The above simulation model based on birth cohort analysis should be useful in estimating the impact of developments in prevention and treatment of lung cancer as well as in predicting the future mortality trend.

Adult↗

"Two-route chemotherapy" using high-dose ip cisplatin and iv sodium thiosulfate, its antidote, for peritoneally disseminated cancer in mice.

We studied the effects of "two-route chemotherapy (TRC)" using cisplatin given ip and its antidote, sodium thiosulfate (STS), given iv on mice bearing peritoneally disseminated cancer. Initially, a pharmacokinetic analysis of cisplatin given ip and STS given iv or sc was made. The plasma concentrations of non-protein-bound and total platinum increased rapidly to a maximum at 10 mins after ip administration of cisplatin alone. When STS alone was given sc, the peak level in the plasma was much lower than that given iv. The superiority of the iv route for STS administration was observed in the lethal toxicity tests. The iv administration of STS to mice 1 min after cisplatin given ip was the best protocol to protect against the lethal toxicity of cisplatin. The protective conditions were applied to TRC in which STS was given iv 1 min after ip cisplatin to mice bearing peritoneally disseminated cancer. Significantly superior antitumor effects were observed in mice given TRC by evaluating survival time as compared with mice given a single treatment with cisplatin at an equitoxic level. The nephrotoxic and hematotoxic effects were slight in TRC.

Animals↗