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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 451 records · Page 25Linked to original sources

Endothelin-1-like immunoreactivity in human urine.

By using a radioimmunoassay specific for endothelin-1 (ET-1), we studied whether ET-1-like immunoreactivity (LI) is present in human urine. Significant amounts of ET-1-LI were present in human urine, and the daily urinary excretion of ET-1-LI in 30 normal subjects was 67.6 +/- 35.5 ng/day. The mean urinary excretion of ET-1-LI determined in spot urine was 82.8 +/- 38.2 pg/mg creatinine (n = 30), while the mean plasma concentrations of ET-1-LI in the same individuals were 1.1 +/- 0.5 pg/ml. There was no significant correlation between urinary ET-1-LI excretion and its plasma levels. Reverse-phase high-pressure liquid chromatography of human urine extract revealed a major ET-1-LI component coeluting with standard ET-1. The present study demonstrates the presence of ET-1-LI excreted in human urine, although its exact source and physiological significance in renal tissues remain to be determined.

Adult↗

Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines.

We studied whether a novel vasoconstrictor peptide, endothelin-1 (ET-1), is synthesized by and released from human carcinoma cell lines, and whether ET-1 stimulates proliferation of these tumor cells. ET-1-like immunoreactivity was released from both HeLa and HEp-2 cells as a function of time. Reverse-phase HPLC of the conditioned media from HeLa cells revealed a major peak coeluting with standard ET-1. Northern blot analysis demonstrated the expression of mRNA for ET-1 precursor in both tumor cell lines. Both cell lines contained a single class of specific binding sites for ET-1. ET-1 dose-dependently induced increases in cytosolic free Ca2+ concentration in fura-2-loaded tumor cells, whose effect was completely abolished by chelating extracellular Ca2+ or by Ca(2+)-channel blocker. ET-1 stimulated proliferation of the quiescent cell lines in a dose-dependent manner, whose effect was inhibited by Ca(2+)-channel blocker. Polyclonal antibody for ET-1 inhibited proliferation of these cell lines, whereas nonimmune serum had no effect. These results demonstrate that ET-1 is synthesized by and released from human epithelial carcinoma cell lines, and that exogenous and endogenous ET-1 stimulates proliferation of the cells possibly through Ca2+ influx, suggesting its role as an autocrine/paracrine growth factor for certain tumor cells.

Calcium↗

Salt sensitivity in Goldblatt hypertensive rats--role of extracellular fluid volume and renin-angiotensin system.

Effects of a high-salt diet on blood pressure, extracellular fluid volume, and the renin-angiotensin system in rats with the two types of Goldblatt hypertension were examined. Both in one-kidney, one clip (1K1C) rats and in one-kidney, sham-clipped (1K) rats, systolic blood pressures of rats which received a high-salt diet for 4 weeks were higher than those of rats of respective groups on a normal-salt diet, suggesting an increased sensitivity of blood pressure to changes in salt intake. Whereas sodium space was increased in 1K rats on the high-salt 1K1C rats receiving the high-salt did not have significantly increased sodium space. These results suggest that acceleration of 1K1C hypertension with salt load could not be explained only by changes in extracellular fluid volume. In contrast, both in two-kidney, one clip (2K1C) rats and in two-kidney, sham-clipped (2K) rats, the high-salt diet produced no change in blood pressure despite the increase in sodium space, suggesting a decreased salt sensitivity. Although on the normal-salt diet the blood pressure of 2K1C rats tended to correlate with plasma renin activity, on the high-salt diet plasma renin activity was markedly decreased, and then blood pressure highly correlated with sodium space. Accordingly, the lesser salt sensitivity in 2K1C rats is probably attributable to the counterbalance of the suppressed renin-angiotensin system against volume expansion. Evidence presented suggests, therefore, that 1K1C rats have greater salt sensitivity of blood pressure than 2K1C rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of cholinergic drugs on delayed discrimination disruption by AF64A in rats].

In a 2-lever operant chamber situation for food reinforcement, the effects of nicotine, arecoline and physostigmine on delayed discrimination responses in rats treated with ethylcholine mustard aziridinium ion (AF64A) were investigated. AF64A at 6 nmol, i.c.v., decreased the percentage of correct choices (% CR) at the delay time of 4 sec, and this effect depended on the delay time. On the other hand, AF64A at the same dose shortened the latency (LAT: the period from the end of the delay time to the initiation of lever-pressing responses) at the delay time of 16 sec, but this effect didn't depend on the delay time. Nicotine at 0.25 mg/kg, s.c., improved the decrease of % CR; and at 0.13-0.5 mg/kg, s.c., it shortened LAT at the delay time of 4 sec in rats treated with AF64A. Arecoline at 4 mg/kg, s.c., and physostigmine at 0.06-0.5 mg/kg, s.c., extended LAT, but both drugs showed no effects on % CR at the delay time of 4 sec in rats treated with AF64A. These results suggest that the present procedure might be useful for the evaluation of drug effects on memory in rats, and nicotine improved the delayed discrimination disruption induced by AF64A.

Animals↗

[Studies on the involvement of the nucleus accumbens in the discriminative effects of nicotine in rats].

The central mechanism mediating the discriminative effects of nicotine was studied using rats. Rats were trained to discriminate subcutaneously administered nicotine at 0.5 mg/kg from saline in a 2-lever operant chamber situation for food reinforcement. 1) Nicotine administered into the lateral ventricle at both 100 micrograms and 120 micrograms substituted for subcutaneously administered nicotine at 0.5 mg/kg. This result indicates that the discriminative effects of nicotine are mediated centrally. 2) Among the drugs, acetylcholine at 0.5-10 micrograms administered into the lateral ventricle and methamphetamine at 5-40 micrograms and dopamine at 1-10 micrograms administered into the nucleus accumbens, none substituted for subcutaneously administered nicotine. These results indicate that the discriminative effects of nicotine differ from those of the above drugs. 3) Nicotine at 100 micrograms administered into the nucleus accumbens almost completely substituted for subcutaneously administered nicotine. In addition, mecamylamine at 180 micrograms administered into the nucleus accumbens attenuated the discriminative effects of subcutaneously administered nicotine. These results suggest that nicotinic receptors in the nucleus accumbens may be involved in the discriminative effects of nicotine. However, further studies are needed, since the nucleus accumbens is regarded not to be a major site of action of nicotine for these effects because of its low susceptibility to nicotine and mecamylamine.

Acetylcholine↗

Effects of MCI-727, a new antiulcer agent, on various gastric and duodenal lesions in experimental animals.

Effects of a new antiulcer drug, MCI-727, on gastric and duodenal lesions, gastric secretion and gastric motility were studied in comparison with cimetidine and teprenone. MCI-727 dose-dependently (3-100 mg/kg, p.o. or i.d.) inhibited the development of acute gastric or duodenal lesions such as pyrolus ligation-, water-immersion stress-, indomethacin-, HCl-, HCl-ethanol-induced gastric lesions and cysteamine-induced duodenal lesions in rats and histamine-induced duodenal lesions in guinea pigs. These antiulcer effects exceeded those of cimetidine or teprenone. Repeated administration of MCI-727 (0.3-3 mg/kg/day, p.o., for 10 days) significantly promoted the spontaneous healing of acetic acid-induced chronic gastric ulcers. Concerning gastric acid secretion, MCI-727 selectively inhibited tetragastrin-stimulated acid secretion without effecting basal acid secretion and acid secretion by other stimuli. Cimetidine and teprenone inhibited acid secretion in several cases. MCI-727 and teprenone had inhibitory effects on gastric motility, although cimetidine had no effect. These results suggest that MCI-727 has a wide spectrum of antiulcer activity, and its mode of antiulcer action is different from that of cimetidine or teprenone.

Animals↗

Appearance of beta-human atrial natriuretic peptide in collagen disease.

To elucidate the circulating forms of human atrial natriuretic peptide (hANP) in collagen disease, we analysed plasma samples obtained from 21 patients with systemic lupus erythematosus, rheumatoid arthritis or progressive systemic sclerosis with no clinical evidence of cardiac involvement. The findings were compared with those obtained from 21 healthy control subjects. Plasma hANP-like immunoreactivity was normal in all but three of the controls and in two patients with the nephrotic syndrome due to lupus nephritis. Reverse-phase high-performance liquid chromatography, gel permeation chromatography and subsequent radioimmunoassay for hANP revealed that the circulating hANP consisted of alpha-hANP, beta-hANP and gamma-hANP in the patients with collagen disease whereas alpha-hANP predominated in the control group. beta-hANP appeared in 18 of the 21 patients but was not observed in the controls. These data suggest that beta-hANP circulates in the plasma of patients with collagen disease even when no myocardial involvement is apparent and that the appearance of beta-hANP is not always associated with an increase in total plasma hANP-like immunoreactivity. Thus the appearance of beta-hANP in plasma is not a phenomenon specific to congestive heart failure.

Adult↗

Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12).

Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B12 (methylcobalamin). A 15-year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000 micrograms/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B12 deficiency or hypothyroidism (which can cause B12 deficiency). Serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B12 and its metabolites is discussed.

Achievement↗

[Central motor conduction time in the pseudopolyneuritic form of amyotrophic lateral sclerosis].

Central motor conduction time (CMCT) from the cerebral motor cortex to the cervical segment of the spinal cord (C-CMCT) and CMCT from the cortex to the lumbar segment of the spinal cord (L-CMCT) were estimated using percutaneous electrical cortical, cervical and lumbar stimulation in 8 patients with pseudopolyneuritic form of amyotrophic lateral sclerosis (ALS). The results were compared to those in 18 patients with bulbar and common forms of ALS and 13 normal control subjects. Both the C-CMCT and the L-CMCT were remarkably prolonged in pseudopolyneuritic form of ALS as well as in bulbar and common forms of ALS. These results were consistent with the morphological findings that the large myelinated fibres in the corticospinal tract are depleted in pseudopolyneuritic form of ALS in which deep tendon reflexes are hypoactive and pyramidal sings are not obvious. The evaluation of CMCT is suggested to be useful for diagnosis of ALS in which upper motor neurone disorder is not manifested.

Adult↗

[Resin adhesion on the young permanent ground enamel (Report 3)].

The purpose of this study was to investigate the influence of thermal cycling on the adhesion of the resin on the young permanent ground enamel which was etched with different etching times. Labial surfaces of 50 extracted and frozen bovine mandibular young permanent incisors were used. The etchant used in this study was 40% phospholic acid gel and the etching times were 0, 10, 20, 30 and 60 seconds. All of the specimens were washed with an air water spray after etching. The bonding agent and composite resin used in this study were Photo Bond and Photo Clearfil A (Kuraray Co.). After thermal cycling tests of 10,000 temperature cycles between 60 degrees C and 4 degrees C water baths, shear bond strengths on the ground enamel were measured. After the shear bond strength tests, all the test surfaces of the enamel and resin specimens were observed using the SEM. The results of this study were compared with the previous results which were not thermal-cycled. The following conclusions were obtained. 1) The etching time which showed the highest bond strength was 30 seconds (45.21 +/- 8.49 Mpa). 2) When the enamel was etched with all of the etching times, the bond strength were significantly higher than that of the enamel without etching. 3) In the etched groups, the bond strength with 20 seconds of etching time was significantly lower than those with 10, 30 and 60 seconds of etching times. 4) In the 10, 30 and 60 seconds etching times, the bond strengths with thermal-cycled groups were significantly higher than those without thermal-cycled groups. 5) On the enamel specimens after the shear bond strength tests, the frequency of the clear prism structures observed on the enamel was higher in the groups which showed higher bond strengths. However, the differences were not significant.

Acid Etching, Dental↗

Chemically induced tumors in transgenic mice carrying prototype human c-Ha-ras genes.

Three independent transgenic mouse lines carrying human prototype c-Ha-ras genes were established. Approximately 50% of the transgenic offspring of these lines developed spontaneous tumors within 18 months. Types of tumors were restricted to angiosarcomas, skin papillomas and lung or Harderian adenocarcinomas. Interestingly, all angiosarcomas (16/16) had point mutations at the 61st codon of the transgenes. Furthermore, they were also very susceptible to the chemical carcinogens, N-methyl-N'-nitrosourea (MNU) and dimethyl-benzanthracene (DMBA). Within 12 weeks after administration of MNU, the transgenic mice developed forestomach papillomas and then carcinomas very frequently, at the rate of almost 100% and almost all of the tumors had point mutations in their transgenes at the 12th codon from GGC (Gly) to GAC (Asp). All the carcinomas of the forestomach, lung and spleen induced by DMBA had point mutations at the 61st codon from CAG (Gln) to CTG (Leu). Because no somatic point mutations in the transgenes have ever been detected in normal tissues of the affected mice, these mutations seemingly activated the human prototype c-Ha-ras transgene. From these results, it is suggested that the somatic mutation of the human c-Ha-ras transgene plays a causative role in the occurrence of natural tumors and those induced by MNU or DMBA administration in transgenic mice. This transgenic mouse provides a unique screening system for chemicals that induce or suppress the tumorigenesis.

Animals↗

Effects of Chinese herbal drug, dai-saiko-to on plasma lipids, lipoproteins and liver lipid contents in guinea pig.

Effects of Chinese herbal drug, Dai-saiko-to, on plasma lipids, lipoproteins and liver lipid contents were investigated in guinea pig with/without cholesterol feeding. Guinea pigs were divided into 4 groups (Group 1: normal chow (N) diet, Group 2: N + 1% Dai-saiko-to (D) diet, Group 3: 1% cholesterol (C) diet, Group 4: 1% C+ 1% D diet), and were treated for 5 weeks. Significant body weight reductions were observed in Groups 3 and 4 compared to Groups 1 and 2. Significant reductions of plasma triglyceride (TG) and very low and low density lipoproteins [(V) LDL]-TG were found in Group 3 compared to Groups 1, 2, and 4. (HDL)-TG significantly decreased in Groups 3 and 4 compared to Groups 1 and 2, but no significant difference was noted between Groups 1 and 2, and Groups 3 and 4. Liver lipid contents analysis showed no significant changes between Groups 1 and 2, and Groups 3 and 4, respectively, but the distribution of lipid droplets as pathologically determined using a computer program showed Group 4 had less lipid deposition compared to Group 3. These data suggest that Dai-saiko-to acts on triglyceride metabolism in hypercholesterolemic guinea pigs.

Alanine Transaminase↗