Biomedical subjects
Publications and source records attributed to K Aoki.
Streptomycin-dependent (SMd) mutant strains of Salmonella typhimurium TA98 and TA100 were isolated. A highly sensitive detection system was obtained by using these SMd derivatives for the SMd leads to SMind mutation. The system was available for testing the mutagenicities of samples containing histidine, such as food.
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The hypotensive effect of acute and longterm, intravenous and oral administration of the calcium antagonist, diltiazem, was investigated in 8 normotensive volunteers and 55 patients with essential hypertension. Diltiazem i.v. infusion of 45 mg/h (0.5 mg/min, then 1.0 mg/min, each for 30 min rapidly decreased both blood pressure (BP) from 164 +/- 22/98 +/- 8 to 144 +/- 15/86 +/- 9 mmHg (mean +/- SD) and total peripheral resistance from 32.6 +/- 8.4 to 25.3 +/- 5.4 mmHg/l/min (p less than 0.001), and increased stroke volume from 58.2 +/- 9.5 to 64.2 +/- 8.6 ml/beat (p less than 0.05). It altered neither heart rate nor cardiac output in the hypertensives (n = 10). Oral diltiazem 60 mg rapidly decreased BP from 155 +/- 10/103 +/- 6 to 142 +/- 12/90 +/- 8 mmHg after 3 hours (p less than 0.01/p less than 0.001) in hypertensives (n = 8), but not in normotensives (n = 8). Diltiazem 90 mg p.o. decreased BP from 157 +/- 15/102 +/- 9 to 129 +/- 13/83 +/- 8 mmHg (p less than 0.01) in hypertensives (n = 15), and reduced the heart rate from 71 +/- 8 to 65 +/- 8 beats/min (p less than 0.01). The drug did not change plasma renin activity either in normotensives or hypertensives. The fall in diastolic BP was correlated with the plasma diltiazem concentration (r = 0.910, n = 6, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The choice of opioid receptor subtype by dynorphins was studied in isolated preparations. Both dynorphin-(1-17) and dynorphin-(1-8) had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum. The inhibition of contractions by dynorphin-(1-17) in three preparations was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors, indicating that dynorphin-(1-17) acted on kappa-receptors in three preparations. Additionally, the inhibitory potency of dynorphin-(1-17) relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in guinea-pig ileum was similar to that in either mouse vas deferens or rabbit ileum. This also suggested that dynorphin-(1-17) acted as a kappa-receptor agonist in three preparations. The effectiveness of naloxone and Mr 2266 to antagonize the agonist action of dynorphin-(1-8) indicated that dynorphin-(1-8) acted as a kappa-receptor agonist in either guinea-pig ileum or rabbit ileum whether or not peptidase inhibitors were existed while in mouse vas deferens it acted as a delta- or kappa-receptor agonist in the absence or presence of peptidase inhibitors, respectively. Thus, the choice of opioid receptor subtype in mouse vas deferens by dynorphin-(1-8) was likely to depend whether peptidases were inhibited or not. The inhibitory potency of dynorphin-(1-8) in the presence of peptidase inhibitors relative to that of ethylketocyclazocine in rabbit vas deferens, which had been shown to contain kappa-receptors exclusively, was similar to that in either mouse vas deferens or rabbit ileum, but was significantly different from that in guinea-pig ileum. This indicates that kappa-receptors in guinea-pig ileum are different from those in other preparations although the possibility of other causes such as incomplete inhibition of peptidase(s) can not be neglected.
X-ray structure analysis of the silver(I) complex of d-(+)-biotin, [Ag(biotin)(NO3)] X 0.5H2O, shows the complex to be polymeric with the silver ion coordinated tetrahedrally to nitrate and to three different biotin molecules. Binding to the latter involves two thioether sulfur atoms in the cis and trans direction with respect to the ureido ring, and one ureido carbonyl oxygen atom. The biotin carboxylate group is probably protonated and not coordinated with the silver ion.
A condition is derived for reciprocal altruism to evolve by kin or group selection. It is assumed that many additively acting genes of small effect and the environment determine the probability that an individual is a reciprocal altruist, as opposed to being unconditionally selfish. The particular form of reciprocal altruism considered is TIT FOR TAT, a strategy that involves being altruistic on the first encounter with another individual and doing whatever the other did on the previous encounter in subsequent encounters with the same individual. Encounters are restricted to individuals of the same generation belonging to the same kin or breeding group, but first encounters occur at random within that group. The number of individuals with which an individual interacts is assumed to be the same within any kin or breeding group. There are 1 + i expected encounters between two interacting individuals. On any encounter, it is assumed that an individual who behaves altruistically suffers a cost in personal fitness proportional to c while improving his partner's fitness by the same proportion of b. Then, the condition for kin or group selection to prevail is [Formula: see text] if group size is sufficiently large and the group mean and the within-group genotypic variance of the trait value (i.e., the probability of being a TIT-FOR-TAT strategist) are uncorrelated. Here, C, Vb, and Tb are the population mean, between-group variance, and between-group third central moment of the trait value and r is the correlation between the additive genotypic values of interacting kin or of individuals within the same breeding group. The right-hand side of the above inequality is monotone decreasing in C if we hold Tb/Vb constant, and kin and group selection become superfluous beyond a certain threshold value of C. The effect of finite group size is also considered in a kin-selection model.
Rorschach tests were performed on patients with primary generalized epilepsy (PGE) and on patients with temporal lobe epilepsy (TLE) combined with generalized tonic-clonic convulsions. Each group consisted of 20 cases and the two groups were matched as closely as possible. Patients with PGE were found to be characterized by variable responses, sensitivity, extroversion and undifferentiated tendencies. Patients with TLE are practical but inefficient and constricted in character. Cases not on medication displayed the same character types. On the basis of the above findings, speculation is made concerning the features of neurotic or psychotic PGE patients.
A competitive enzyme immunoassay for methamphetamine with alkaline phosphatase labeled methamphetamine, Sepharose-antibody and p-nitrophenylphosphate as substrate was developed. The anti-methamphetamine antisera produced in rabbits by immunization with N-(4-aminobutyl) methamphetamine-BSA conjugate were specific for methamphetamine and showed low cross-reactivities with p-OH methamphetamine and amphetamine (metabolites of methamphetamine). The range of methamphetamine measurable by the enzyme immunoassay was 1 to 300 ng/tube. According to the assay, methamphetamine could be detected from urine and extract of hair.
From June, 1977 to August, 1981, 388 patients underwent open heart surgery for acquired valvular heart diseases. The over-all surgical mortality rate during this period was only 4%, but a high incidence of postoperative complications (26% for major complications) was still observed. It is an urgent concern for all cardiac-surgeons to reduce postoperative complications in order to obtain better surgical results. Even with improved techniques in modern cardiac surgery, 28 patients with a giant left atrium were still in the high risk group, with an over-all mortality rate of 29% and with a high incidence (68%) of postoperative complications. This seemed to be attributable mainly to deteriorated conditions such as cardiac cachexia, but not necessarily to impaired pulmonary function. Therefore, more careful considerations should be paid not only for their circulatory and pulmonary conditions, but also for the improvement of their general condition, including nutrition and metabolism. On the other hand, 27 patients with infective endocarditis showed a remarkable improvement after prosthetic valve replacement in spite of their seriously deteriorated preoperative condition. There were 4 hospital deaths (15% mortality). All transferred to our institution in a far advanced stage of the disease. Early surgical intervention for intractable cardiac failure should be strongly recommended for these patients.
The blood pressure (BP) response to supine rest for one hour and to an isometric handgrip exercise (3 min, 30%, of maximum) was investigated in 18 healthy normotensive men (N) (casual BP 117 +/- 6 / 73 +/- 5 mmHg, 39 +/- 3 years old) (mean +/- SD) and 50 men with essential hypertension (H) (162 +/- 13 / 105 +/- 9 mmHg, 41 +/- 4 years old). Casual BP was decreased by rest to resting BP (113 +/- 7 / 70 +/- 7 in N and 140 +/- 15 / 93 +/- 11 mmHg in H). H was divided into 3 groups of H-1 (resting BP of 124 +/- 7 / 80 +/- 4 mmHg), H-2 (137 +/- 9 / 92 +/- 4) and H-3 (154 +/- 10 / 104 +/- 4). The decreases in BP with rest were significantly greater in Groups H-1 (30 mmHg in systole / 20 mmHg in diastole, p less than 0.001), H-2 (23/11, p less than 0.001) and H-3 (16/8, p less than 0.001/0.05) as compared with those in N (4/3), and this decrease significantly correlated with the resting systolic BP in H (r = -0.601, p less than 0.001) and with diastolic BP (r = -0.604, p less than 0.001). The handgrip exercise increased BP (42/28, 55/35, 39/26 and 30/26 mmHg in Groups H-1, H-2, H-3 and N, respectively). The increase in systolic BP was significantly greater in Groups H-1, H-2 and H-3 than in N (p less than 0.001, p less than 0.001 and p less than 0.01, respectively), and the increase in diastolic BP was significantly greater in Group H-2 than in N (p less than 0.05), but not in Groups H-1 and H-3. The significant decrease in BP with rest and the significant increase in BP by the exercise may represent the pathophysiological nature of the cardiovascular response in the early stage of essential hypertension.
In a 26-year-old male with 17 alpha-hydroxylase deficiency, endocrinological examinations were performed not only after, but also before the onset of clinical signs and symptoms. In addition, the pathophysiological role of the renal kallikrein-kinin system was investigated in this patient. In spite of the fact that this disease is congenital, in the mechanism of its onset, this patient had a period of endocrinological normality before onset; that is, 9 months before onset, both ACTH and cortisol were within the normal range, although the former would be significantly higher and the latter significantly lower than normal values after the onset. In this case, both urinary kallikrein and kininase excretions abnormally increased and then returned to normal after dexamethasone treatment.
We studied the restriction endonuclease cleavage patterns of DNAs of adenovirus type 8 (Ad 8) isolated from epidemic keratoconjunctivitis cases. DNAs of 25 Ad 8 isolates collected during the period from 1975 to 1981 in Sapporo were subjected to enzymatic cleavage with PstI, BamHl , HindIII and SalI. On the basis of the cleavage patterns, the isolates were divided into two subtypes, A and B, both different from Trim strain used as the Ad 8 prototype strain. Subtype A was prevalent in the period from 1975 to 1978, while subtype B in the period from 1976 to 1981.
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The efficacy of "two-route chemotherapy (TRC)" using a combination of cisplatin (DDP) and its antidote, sodium thiosulfate (STS), was evaluated in rat bladder tumor. TRC in which 20 mg/kg of DDP and two doses of 1054 mg/kg of STS (100-fold molar ratio to DDP) were given during interruption of arterial flow for 30 minutes through the abdominal aorta and femoral vein, respectively, provided significantly better antitumor effects evaluated by tumor weight and survival time than did intra-arterial or iv DDP (4 mg/kg) without STS. These three modalities revealed a similar toxicity in rats. Dose- and time-related efficacy of DDP and a high sensitivity of a transitional cell carcinoma of the rat to DDP were noted in TRC. Nephrotoxicity assessed by increase in BUN levels was minimum. The particular combination of intra-arterial DDP and iv STS presented here is applicable to regionally confined human bladder cancer.
Ceftazidime (CAZ), a new cephalosporin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of CAZ into intrapelvic genital organs were good after a single drip infusion of 1.0 g for 30--60 minutes. The maximum level of 76.4 micrograms/ml was obtained in uterine artery serum at 8 minutes after administration. The high concentrations were also obtained in genital tissues; the maximum concentrations ranged from 46.8--62.1 micrograms/g at 20 minutes after administration and the levels were as high as 2.1--7.7 micrograms/g at 5 hours and 40 minutes after administration. The concentration curves in tissues were consistent with those of serum levels. The concentrations of CAZ in retroperitoneal dead space exudate were determined after intravenous drip infusion of 1 g. The peak levels ranged from 26 to 32 micrograms/ml after 30 minutes of administration and the level of 8.53 micrograms/ml was sustained even 6 hours later. Good response was obtained in cases of gyneco-obstetric infections such as intrauterine infection, intrapelvic infection and external genital infection with daily dose of 2--4 g. CAZ was effective in 13 out of 14 cases (the efficacy ratio; 92.9%). As to side effects, gastric discomfort and vomiting were observed in 1 case.
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