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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 739 records · Page 41Linked to original sources
PubMed1986

"Two-route chemotherapy" using high-dose intra-arterial neocarzinostatin and systemic tiopronin, its antidote, for rat limb tumor.

We studied the effect of "two-route chemotherapy" (TRC) with intra-arterial (IA) neocarzinostatin (NCS) and IV N-(2-mercaptopropionyl)-glycine (tiopronin), its antidote, on rat limb tumors. Chemotherapy experiments were carried out on day 9 after the inoculation of 10(6) syngeneic transitional carcinoma cells into the hind limb in female Wistar King A rats. In the group given TRC, 3500 units/kg NCS and 800 mg/kg tiopronin were given via the femoral artery and the femoral vein, respectively. The antitumor effect was evaluated by the tumor weight on day 12 after the treatment. Compared with the weight of tumors in untreated controls, TRC reduced tumor weight to one-tenth, while 700 units/kg IA NCS alone reduced tumor weight to one-third and 700 units/kg systemic NCS alone reduced tumor weight to three-fourths of the control weight. In the group given TRC, WBC and nucleated bone marrow cells were completely protected and loss of body weight was slight.

Animals↗
PubMed1986

Circadian, sleep and brain temperature rhythms in cats under sustained daily light-dark cycles and constant darkness.

In adult cats, sleep-wake states and brain temperatures were determined under experimental LD cycles and prolonged DD. Convincing rhythms had not previously been well-established for this animal. The present results demonstrated daily fluctuation in total sleep time (TST) and in brain temperature (Tb). These comprise predominantly nocturnal wakefulness and high temperatures but include a bi-modal component marking dawn and dusk peaks. In addition there are ultradian variations with a period of 2-4 hour superimposed on the circadian rhythm. The latter continued at the beginning of prolonged DD, but gradually diminished and disappeared after about ten days. The TST circadian rhythm diminished more quickly than the Tb rhythm. This result suggests that the former is coupled more strongly to the circadian oscillator than the latter, and that the brain temperature rhythm could not depend on the circadian rhythm of sleep-wakefulness. These results encourage use of cats in further chronobiological studies of sleep and other physiological rhythms.

Activity Cycles↗
PubMed1986

Characterization and biological effects of recombinant human erythropoietin.

Human recombinant erythropoietin (rHuEPO) has been purified to apparent homogeneity and compared to purified human urinary erythropoietin (EPO). Both the purified natural and recombinant EPO preparations were characterized in a competition radioimmunoassay (RIA), the exhypoxic polycythemic mouse bioassay, in vitro tissue culture bioassays using bone marrow cells, and by Western analysis. In the immunological and biological activity assays, the rHuEPO shows a dose response which parallels that of the natural hormone. By Western analysis, the recombinant and human urinary EPO migrate identically. Administration of rHuEPO increases the hematocrit of normal mice in a dose-dependent manner. Additionally, the rHuEPO is able to increase the hematocrit of rats made uremic as a result of subtotal nephrectomy. In summary, by all criteria examined, the rHuEPO is biologically active and equivalent to the natural hormone.

Animals↗
PubMed1986

A stochastic model of gene-culture coevolution suggested by the "culture historical hypothesis" for the evolution of adult lactose absorption in humans.

A stochastic model of gene-culture coevolution, suggested by the "culture historical hypothesis" of Simoons and McCracken, is presented. According to this hypothesis, adult lactose absorption, believed to be an autosomal dominant trait, attained a high frequency in some human populations due to the positive selection pressure induced by culturally determined milk use in those populations. Two-dimensional Kolmogorov backward equations with appropriate boundary conditions are derived for the ultimate fixation probability of milk users, of the gene for adult lactose absorption, and of both jointly, and for the average time until fixation of the gene. These boundary value problems are solved numerically by the Gauss-Seidel method. I define a theoretical measure of the correlation between gene and culture in terms of the three ultimate fixation probabilities. Monte Carlo simulations are conducted to check and extend the numerical results and also to obtain the first arrival time at gene frequency 0.70, which is approximately the highest observed frequency in any population. Two results that pertain to the culture historical hypothesis are obtained. First, the incomplete correlation observed between adult lactose absorption and milk use does not necessarily constitute evidence against the hypothesis. Second, for the postulated genetic change to have occurred within the 6000-year period since the advent of dairying, either the effective population size was of the order of 100, or, if it was of larger order, the selection coefficient probably had to exceed 5%.

Animals↗
PubMed1986

Intermolecular relations of the photosystem II complex in spinach chloroplasts as detected by immunochemical assay.

Polyclonal antibodies were prepared to the subunits of the spinach photosystem II fraction (PS II): p47, p43, p27, p33, p24, and p17. (The protein nomenclature refers to Mr). p47 and p43 are the subunits of reaction center complex, and p27 is light-harvesting chlorophyll protein. p33, p24, and p17 are extractable from PS II with 1 M Tris, and p24 and p17 with 1 M NaCl. With untreated PS II fractions, the antibody to p24 inhibited the photosynthetic oxygen-evolving activity, but not the DCPI-photoreduction activity in the presence of DPC, indicating that p24 played an important role in the former activity. Bindings of the respective antibodies to the PS II treated with sodium dodecyl sulfate were regarded as 100%. To untreated PS II, the bindings were 20-30% for p47, p43, and p27, about 50% for p33, and 70-80% for p24 and p17. To NaCl-washed PS II, the binding to p33 increased by 9%, indicating that p33 was adjacent or bound with p24 or/and p17. To Tris-washed PS II, the binding to p43 increased by 7%, indicating that p43 was adjacent or bound with p33. To PS II treated with 3% of Brij 58, only the binding to p27 increased appreciably. To PS II treated with 1% of octyl glucoside, the binding to p47 was still lower than 50%, whereas those to the other subunits were 74-91%. These values could be a measure of the extents to which the subunits were exposed to the aqueous phase, because of the nature of polyclonal antibodies. These results suggest that in intact PS II, p47, p43, and p27 were in most part buried in the inside, p47 being located at the most central and p27 at the outermost part, whereas p33, p24, and p17 were exposed to the outside by 50-75%.

Antibodies↗
PubMed1986

Effects of NaCl and glycerol on photosynthetic oxygen-evolving activity with thylakoid membranes from halophilic green alga Dunaliella tertiolecta.

It is known that the halophilic green alga Dunaliella tertiolecta grows under hypertonic conditions (with NaCl), which induce the intracellular accumulation of high concentrations of glycerol in order to counterbalance the osmotic change. The effects of NaCl and glycerol on the photosynthetic oxygen-evolving activity of thylakoid membranes prepared from D. tertiolecta were investigated in relation to the dissociation of the membranes. It was found that proteins with Mr of 24,000, 17,000, and 13,000 were dissociated from thylakoid membranes of D. tertiolecta by washing with 1 M NaCl, whereas the photosynthetic oxygen-evolving activity was stimulated 2-fold by 0.1-1.5 M NaCl. The antibodies against spinach 24K and 17K proteins did not cross-react with Dunaliella 24K and 17K proteins, respectively. The salt-tolerant feature of the oxygen-evolving activity with Dunaliella thylakoid membranes may be related to the difference of the properties of these two proteins between D. tertiolecta and spinach. When the membranes were washed with 1 M Tris, proteins with Mr of 50,000 and 31,000 were also dissociated in addition to the 24K and 17K proteins described above. The antibody against spinach 33K protein cross-reacted with 31K protein of D. tertiolecta, showing that Dunaliella 31K protein corresponds to spinach 33K protein. When the membranes were treated with a mixture of 1% cholate and 2% deoxycholate, the oxygen-evolving activity was completely depressed, but the depressed activity was significantly restored by organic solvents. Glycerol and dimethylsulfoxide were the most effective for the restoration.(ABSTRACT TRUNCATED AT 250 WORDS)

Chlorophyta↗
PubMed1986

Effects of Bay K 8644 and nifedipine on femoral arteries of spontaneously hypertensive rats.

Vasoconstrictor effects of Bay K 8644 (an agonist known to increase Ca2+ influx through the voltage-dependent Ca2+ channels) on femoral arteries of 6 week old spontaneously hypertensive rats (SHR) were investigated, and data compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). The addition of Bay K 8644 (1 X 10(-10)-3 X 10(-7) M) elicited a dose-dependent contraction in SHR femoral artery in the absence of any contractile agent. Maximum contraction induced by this agonist was the same as the maximum induced by either K+-depolarization or alpha-adrenoceptor stimulation. Bay K 8644 was less effective in eliciting a contraction in the WKY femoral artery. Increased sensitivity to K+ was also observed in the SHR femoral artery. In contrast, contractions in response to alpha-adrenoceptor stimulation were the same in the SHR as those in the WKY. The addition of nifedipine, a Ca2+ channel antagonist, to an unstimulated preparation produced a dose-dependent relaxation in femoral arteries from SHR, but not from WKY. When the arteries were contracted with 60 mM K+, nifedipine produced similar relaxations in the SHR as those in the WKY, suggesting that the Ca2+ channels in the SHR femoral arteries are more activated than those in the WKY femoral arteries. Contractile responses to SHR femoral arteries to Bay K 8644 were antagonized competitively by nifedipine. Contractile responses to Ca2+ determined in K+-depolarized strips were also antagonized competitively by nifedipine. However, Schild plot analysis demonstrated a different pA2 value for nifedipine, suggesting that there may be a difference in the state of voltage-dependent Ca2+ channels in SHR femoral artery between the stimulation with Bay K 8644 and K+-depolarization.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Sympathetic nerve activity, plasma renin activity and water-sodium balance in obese patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium metabolism on the hypertensive mechanisms in obese patients with essential hypertension (EHT). The obesity index correlated positively with the mean arterial pressure, plasma volume, extracellular fluid volume or total exchangeable sodium, and negatively with plasma noradrenaline concentration or plasma renin activity in EHT. Hypotensive effects of sodium restriction (Na 35 mEq, K 75 mEq) or the natriuretic response to infused dopamine (3 micrograms/kg/min) was remarkable in obese EHT. Fractional excretion of sodium (FENa), which reflects the renal tubular reabsorption of sodium, was significantly lower in obese EHT than that in non-obese or mildly obese EHT. Urinary excretion of free dopamine (UDA) had a positive relationship with simultaneously measured urinary excretion of sodium or FENa. In addition, UDA correlated positively with the obesity index in patients whose weight was under 115% of the ideal weight. On the contrary, the relation between the two parameters was significantly negative in patients whose weight was over 115% of the ideal weight. These findings suggest that the expansion of body fluid volume and sodium, which might result from the blunted natriuretic ability, at least in part, due to an attenuation of the renal dopaminergic activity, play an important role of the hypertensive mechanisms in obese EHT.

Adult↗
PubMed1986

The inactivation of [Met5]-enkephalin by bestatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A and thiorphan-sensitive endopeptidase-24.11 in mouse vas deferens.

The enkephalin-hydrolyzing peptidases in mouse vas deferens were studied and compared with those in guinea pig ileum which had been characterized in the previous study. The present results showed that three distinct peptidases, bestatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and thiorphan-sensitive endopeptidase-24.11, played a critical role in the inactivation of enkephalin in mouse vas deferens, being consistent with the previous results obtained with guinea pig ileum. However, the data in both previous and present studies showed that the activity of the bestatin-sensitive aminopeptidase relative to that of either the captopril-sensitive peptidyl dipeptidase A or the thiorphan-sensitive endopeptidase-24.11 in guinea pig ileum was higher than that in mouse vas deferens, while the activity of either peptidyl dipeptidase A or endopeptidase-24.11 relative to that of aminopeptidase in mouse vas deferens was higher than that in guinea-pig ileum. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase were suggested not to be involved significantly in the inactivation of enkephalin in mouse vas deferens as well as guinea pig ileum.

Amino Acids, Sulfur↗
PubMed1986

Agonist and antagonist actions of buprenorphine on three types of opioid receptor in isolated preparations.

Both agonist and antagonist actions of buprenorphine on isolated preparations were studied. The Ke (equilibrium dissociation constant) values of both naloxone and Mr 2266 [(-)-2-(3-furylmethyl)-5, 9-diethyl-2'-hydroxy-6,7-benzomorphan] against buprenorphine and the ratio of IC50 (concentration of the drug to produce 50% inhibition of the twitch) value of buprenorphine after to before exposure of mouse vas deferens to beta-FNA (beta-fumarate methyl ester derivatives of naltrexone), an irreversible mu antagonist, suggest that buprenorphine acts as both a mu and kappa agonist on mouse vas deferens. The agonist effect of buprenorphine at relatively high doses on guinea-pig ileum and mouse vas deferens and the negative agonist effect on both rat and rabbit vas deferens indicate that buprenorphine acts as a partial agonist on isolated preparations. The Ke values of buprenorphine show that buprenorphine has about equal antagonist effectiveness against a mu and kappa agonist with approximately five-fold lower effectiveness against a delta agonist. The possible mechanisms for the several characteristic actions of buprenorphine on guinea-pig ileum such as the slow onset of action, the increased magnitude of inhibition after washing the tissue, the negative elimination of the inhibition by either washing the tissue or the naloxone administration, and the negative elimination of the antagonist action by washing the tissue were discussed.

Animals↗
PubMed1986

The relative potency of enkephalins and beta-endorphin in guinea-pig ileum, mouse vas deferens and rat vas deferens after the administration of peptidase inhibitors.

Previous studies have shown that three distinct enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and phosphoramidon-sensitive endopeptidase-24.11, played a critical role in the inactivation of enkephalins in isolated preparations. In the present study, therefore, the rank order of the potency of three endogenous opioid peptides, [Met5]-enkephalin, [Leu5]-enkephalin, and beta-endorphin, in three isolated preparations, guinea-pig ileum, mouse vas deferens, and rat vas deferens, was estimated in the presence of the mixture of three peptidase inhibitors, amastatin, captopril, and phosphoramidon. [Met5]-Enkephalin was approximately three-fold more potent than [Leu5]-enkephalin and four-fold more potent than beta-endorphin in guinea-pig ileum in which three opioid peptides were indicated to act on mu-receptors. Additionally, [Met5]-enkephalin was slightly but significantly more potent than [Leu5]-enkephalin and approximately twenty-fold more potent than beta-endorphin at delta-receptor sites in mouse vas deferens. Moreover, [Met5]-enkephalin was approximately three-fold more potent than [Leu5]-enkephalin, but sixty-fold less potent than beta-endorphin in rat vas deferens in which the opioid-receptor type interacting with enkephalins could not be determined. In conclusion, the well-known rank order of the potency of three endogenous opioid peptides was shown to be altered in both guinea-pig ileum and mouse vas deferens but not in rat vas deferens by the pretreatment of the preparations with the mixture of three peptidase inhibitors.

Animals↗
PubMed1986

The enhancing effects of amastatin, phosphoramidon and captopril on the potency of [Met5]-enkephalin in rat vas deferens.

The enkephalin-inactivating enzymes in rat vas deferens were studied by using the relatively specific inhibitor of each enzyme. The results showed that the rat vas deferens, like the other three preparations, guinea-pig ileum, mouse vas deferens and striatal membranes of guinea-pig brain, which had been investigated previously, contained three distinct enkephalin-hydrolyzing peptidases. Additionally, the enkephalin-hydrolyzing aminopeptidase, endopeptidase-24.11 and peptidyl dipeptidase A in rat vas deferens were found to be inhibited maximally with 1 microM of amastatin, 1 microM of phosphoramidon and 1 microM of captopril, respectively. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase were suggested not to be involved significantly in the inactivation of exogenously given enkephalin in rat vas deferens. The characteristics of the enkephalin-degradative enzymes in rat vas deferens were discussed in terms of their similarities to and differences from those in the other preparations.

Animals↗
PubMed1986

Effect of middle ear infection upon the pneumatization of the mastoid: an experimental study in pigs.

The suppression of the temporal bone's pneumatized cavities is commonly observed in chronic middle ear inflammatory disease, but this fact has not been explained in respect to its etiology, i.e., whether the poorly pneumatized cavity induces chronic middle ear infection or middle ear inflammatory condition suppresses the pneumatization of cellulae. We studied the effect of middle ear infection and eustachian tubal dysfunction in the early stage of life upon the development of pneumatization of the mastoid using 13 pigs, whose mastoid is comparable to that of man. We used two methods, the eustachian tube stenosis test and the tympanic membrane paraffin infusion test. The present study indicated that in six pigs infection of the middle ear in the early stage of life suppressed the normal development of pneumatization of the mastoid bone in pigs.

Animals↗
PubMed1986

Decrease in blood pressure and increase in total peripheral vascular resistance in supine resting subjects with normotension or essential hypertension.

Hemodynamic changes in the supine resting position were investigated in 70 male subjects, consisting of 15 healthy volunteers with normotension (blood pressure of 113 +/- 7/70 +/- 5 mmHg, M +/- SD), 25 patients with borderline essential hypertension (143 +/- 12/90 +/- 6 mmHg) and 30 patients with established essential hypertension (166 +/- 13/108 +/- 6 mmHg). The supine position reduced blood pressure, heart rate, stroke volume and cardiac output (p less than 0.001), but increased total peripheral vascular resistance (p less than 0.001). The decrease in systolic blood pressure (p less than 0.01), stroke volume (p less than 0.05) and cardiac output (p less than 0.05), and the increase in total peripheral vascular resistance (p less than 0.01) were significantly greater in the borderline and established essential hypertensive groups than in the normotensive group. The results demonstrated that the decrease in blood pressure was due to a reduction in both heart rate and stroke volume, and that the decrease in stroke volume and increase in total peripheral vascular resistance seen in the supine position were greater in the hypertensive groups than in the normotensive group. These hyperresponses may contribute to the development and persistence of high blood pressure in patients with essential hypertension.

Adult↗
PubMed1986

Hypotensive effects of a calcium antagonist, bepridil, in patients with essential hypertension.

The short and long term hypotensive effects of oral administration of bepridil were investigated in 26 patients with essential hypertension. A new calcium antagonist, bepridil inhibits the ion influx through sodium and potassium channels as well as calcium channels by directly affecting these channels. The drug (150 mg) rapidly decreased blood pressure (BP) from 157 +/- 12/97 +/- 8 to 137 +/- 10/86 +/- 8 mmHg (mean +/- SD, p less than 0.01) and heart rate (HR) from 64 +/- 5 to 58 +/- 4 beats/min (p less than 0.01) (n = 6) in 2 hours. Long term administration of 150 mg bepridil daily (50 mg t.d.s.) decreased BP from 169 +/- 6/104 +/- 8 to 143 +/- 14/83 +/- 7 mmHg (p less than 0.001), but did not change HR (66 +/- 4 and 67 +/- 5 beats/min, before and after administration) (n = 9). Bepridil at 300 mg (100 mg t.d.s.) decreased BP from 172 +/- 15/105 +/- 8 to 146 +/- 11/88 +/- 4 mmHg (p less than 0.001) and HR from 76 +/- 11 to 70 +/- 8 beats/min (p less than 0.01) (n = 9). No side effects were observed. In conclusion, the hypotensive and negative chronotropic actions of bepridil are beneficial in the short and long term treatment of essential hypertension.

Administration, Oral↗