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Biomedical subjects

K Eto

Publications and source records attributed to K Eto.

At least 19 recordsLinked to original sources

Effects of exposure to cigarette smoke on intestinal propulsion in rats.

The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.

Animals

Apical cell escape from the neuroepithelium and cell transformation during terminal lip fusion in the house shrew embryo.

The house shrew embryo has many cells in the ventricular lumen and on the luminal surface of the fusing terminal lip of the cephalic neural tube. The origin and fate of these cells were studied by means of light and electron microscopy, and by DiI labeling in a whole-embryo culture system. The cells appeared at stage 11A and persisted until stage 12A. Most of the cells seemed to originate from the neuroepithelium, as shown by frequent observations of epithelial cell escape and DiI labeling analysis. The cells on the luminal surface sometimes showed apoptotic features, but were not subjected to phagocytosis. Some of the escaping cells seemed to migrate to the ventral part of the prosencephalic neuropore and insert themselves into it. Others separated from the luminal surface and floated into the lumen. It seems likely that the floating cells either become autolyzed, or else change into macrophage-like cells, the latter alternative being supported by the results of DiI labeling. The macrophage-like cells actively phagocytosed the other degenerating cells and apoptotic bodies. These observations suggest that the apical escape of cells may play an important role in the remodeling of the neural fold during the terminal lip fusion, and that early neuroepithelial cells may have the potential to become cells with vigorous phagocytic activity, like macrophages.

Animals

Thimerosal induces toxic reaction in non-sensitized animals.

The effects of injection of thimerosal solution on nonsensitized animals was investigated. Intrafootpad injection of thimerosal solution in nonsensitized mice resulted in a swelling response which peaked 1 h after injection and lasted for more than 24 h. Histopathological examination showed that there were severe edema and infiltration of polymorphonuclear neutrophils at the site of injection. An increased vascular permeability was observed after cutaneous injection of thimerosal solution on the back of nonsensitized rats. Since mercuric chloride and methyl mercury induced severer reactions, and thiosalicylic acid had no effect, mercury contained in thimerosal would have caused the reactions observed in this study. These results suggest that part of these hypersensitivity reactions against thimerosal observed among patients were possibly induced by the toxic effect of thimerosal. Therefore, thimerosal contained as a preservative in vaccine may augment the side-effects of the vaccination.

Animals

Influences of exposure to cigarette smoke on concentration of nicorandil in plasma of rats.

Influences of acute exposure to cigarette smoke on plasma concentrations of nicorandil administered orally and parenterally were investigated in rats by HPLC. The animals were exposed to tobacco smoke of two kinds of cigarettes using a smoking machine (i.e., the cigarette smoke contained either low or high nicotine and tar). The plasma concentration of nicorandil administered orally at a dose of 10 mg/kg had a lower absorption phase in two cigarette smoke-exposed groups, particularly in the high nicotine and tar-containing cigarette smoke-exposed group, compared with the nonsmoking control group. The AUC and MRT values in a high nicotine and tar-containing cigarette smoke-exposed group were lower and higher, respectively, than in the nonsmoking control group. However, there was no marked difference in nicorandil plasma concentrations between the cigarette smoke-exposed group and the nonsmoking control group when nicorandil was administered ip or iv at a dose of 5 mg/kg. These results suggest that cigarette smoke exposure causes the suppression or delay of absorption of nicorandil from the gastrointestinal tract.

Administration, Oral

Effects of exposure to standard- and nicotine-reduced-cigarette smoke on pharmacokinetics of theophylline and cimetidine in rats.

Influences of exposure to standard- (containing nicotine and tar) and nicotine-reduced-cigarette smoke on the pharmacokinetics of theophylline (20 mg/kg, per os) and cimetidine (50 mg/kg, per os) were investigated in rats. Animals were exposed to standard- or nicotine-reduced-cigarette smoke for 8 min with a "smoking machine". In control rats, theophylline concentrations in plasma increased rapidly, peaked 2 h later, and then decreased gradually. Concentrations of theophylline in plasma of rats exposed to standard- and nicotine-reduced-cigarette smoke were suppressed in comparison with that of control rats, and the suppressive effect of nicotine-reduced-cigarette smoke was weaker than that of standard-cigarette smoke. The suppression of theophylline concentrations in plasma induced by exposure to cigarette smoke may be due to nicotine and other constituents of the cigarette smoke, even if the effects are slight. For cimetidine, no difference was found between drug concentration in plasma of rats exposed to nicotine-reduced-cigarette smoke and that of control rats; however, the drug concentration in plasma of rats exposed to standard-cigarette smoke was markedly suppressed. These results suggest that the suppression of cimetidine concentrations in plasma may be due solely to nicotine in cigarette smoke.

Animals

Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus.

Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. We isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, we identified a missense mutation substituting arginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM).

Base Sequence

Influences of long-term cigarette smoke exposure on pharmacokinetics of theophylline, and on liver microsomal enzymes in rats.

The influences of long-term cigarette smoke exposure on pharmacokinetics of oral theophylline (20 mg/kg), and on liver microsomal enzymes which metabolize drugs were studied in rats. Animals were exposed to cigarette smoke for 20 min each in the morning and evening every day for 26 days in the pharmacokinetic study, and 27 days for the enzyme assays. Theophylline was administered 13 h after the last exposure to smoke, and plasma concentrations were measured using HPLC. Plasma concentrations of theophylline during the absorption phase and 6 h after oral administration were lower in the long-term cigarette smoke-exposed group than in the control group. In the smoke-exposed group, the AUC and Ka were lower, and the Ke was slightly higher than in the control group. Liver weight and the ratio of liver weight to body weight were lower in the smoke-exposed group, and cytochrome b5 content and NADPH-cytochrome P-450 reductase activity were higher, but cytochrome P-450 content did not differ from the control group. These results indicate that long-term exposure to cigarette smoke suppresses theophylline absorption from the gastrointestinal tract, accelerates its elimination, and affects liver microsomal enzymes which metabolize drugs.

Animals

Different susceptibilities to attenuated poliovirus of cynomolgus monkeys from the Philippines and other Southeast Asian countries.

Susceptibilities to attenuated poliovirus of cynomolgus monkeys were assessed by the intraspinal inoculation method with the same single bulk lot as the reference for each of the three poliovirus types. The lesion-inducing virus dose in the spinal cord of 50% of monkeys inoculated (LID50) varied widely from 10(6.4) to lower than 10(2.5), the difference being as much as 10,000-fold, depending on the birth place of the monkey. The birth places of the monkeys used were traced and categorized into the following three districts; the peninsular region, Indonesia and the Philippines. The LID50 value of the attenuated poliovirus in the monkeys from the Philippines were much lower than those in the monkeys from the other two districts.

Animals

Comparative studies of embryotoxic action of ethylenethiourea in rat whole embryo and embryonic cell culture.

The effects of ethylenethiourea (ETU) were investigated using rat (Wistar-imamichi) embryos cultured from days 11 to 13 of gestation or cultured rat embryonic cells extracted on day 11. Malformations in cultured embryos at the concentration of 30 micrograms/ml of ETU were found in the head and tail, which were severely affected, as well as the limb and face. All embryos exposed to 150 and 300 micrograms/ml of ETU had malformed heads, tails, limbs, and facial configurations. Protein contents of the cultured embryos were decreased dose-dependently at the concentrations ranging from 30 to 300 micrograms/ml. In the histological studies of the cultured embryos with ETU, thinner neuroepithelium in head was observed. In the embryonic cells extracted on day 11 of gestation, ETU dose-dependently inhibited the differentiation of midbrain (MB) cells into neurons and that of limb bud (LB) cells into chondrocytes at the concentrations ranging from 30 to 600 micrograms/ml of ETU. The concentrations of ETU that inhibited the production of differentiated foci by 50% (IC50) were 170 micrograms/ml in LB cells of day 11, and greater than 600 micrograms/ml in LB cells on day 12 of development. Therefore, differentiation of MB cells was more sensitive to ETU than the differentiation of LB cells. These results indicated that there was a reasonable correlation of ETU induced changes in cultured whole embryos and embryonic cells.

Abnormalities, Multiple

Age- and sex-related differences in the nerve growth factor distribution in the rat brain.

Levels of the nerve growth factor (NGF) have been measured in various brain regions of young and aged male and female rats of Wistar strain by means of a highly sensitive two-site enzyme immunoassay system for beta-NGF. Among the ten regions examined, the amount of NGF per wet weight of tissue was found to be highest in the hippocampus, irrespective of the sex and age. The NGF concentration in the hippocampus of female rats at 3 months of age was comparable to that of same aged males. Further, there was no significant difference in the NGF levels of the hippocampus between young and age males. However, the NGF level was significantly lower in aged females as compared to that in 3- or 4-month-old females, and hence the marked male-female difference was found in the NGF levels in aged Wistar rats.

Aging

Analysis of prognostic factors in patients with pyeloureteral carcinoma.

Clinicopathological parameters and therapeutic results of 100 patients with primary pyeloureteral cancers were examined, and prognostic factors were identified by monovariable and multivariable analyses. For the whole group, the 5- and 10-year survival rates were 57.0% and 44.8%, respectively. The site-specific 5-year survival rates were 61.0% for pelvic cancer, 51.9% for ureteral cancer, and 61.7% for pyeloureteral cancer, showing no significant differences among the sites. Monovariable analysis indicated age, tumor form, and histological stage and grade as important prognostic factors. Using multivariable analysis, concurrence of bladder cancer, age, histological stage, radiotherapy, surgery, chemotherapy, and histological grade were shown to be prognostic factors, given in order of decreasing importance. Age and histological stage, which were common to the results of both analyses, were considered to be most important as prognostic factors.

Adult

Immunohistochemical characterization of multinucleated giant cells in the brain of a Japanese AIDS patient.

In an autopsy case of a 35-year-old Japanese hemophiliac with acquired immune deficiency syndrome (AIDS), many multinucleated giant cells (MGCs) were observed throughout the central nervous system. Immunohistochemically, MGCs possessed surface and cytoplasmic macrophage antigens expressed in the late stage of differentiation indicating them to be macrophages in the terminal stage of differentiation. Fine nuclear extensions connecting one nucleus (or lobe) to another were often observed in the MGCs. This feature was interpreted as multilobulation and considered to be a morphological characteristic of MGCs in AIDS encephalopathy. Similarity between MGCs in AIDS encephalopathy and highly lobulated lymphocytes in adult T cell leukemia is discussed.

AIDS Dementia Complex

Effect of cigarette smoking on theophylline pharmacokinetics in rats.

The effect of acute cigarette smoke inhalation on the plasma levels of theophylline administered orally and parenterally to rats has been studied. The animals were exposed to smoke containing low- or high-nicotine/tar concentration for 10 min immediately after oral, intraperitoneal (i.p.) or intravenous (i.v.) administration of theophylline. The plasma levels of theophylline when administered orally (20 mg kg-1) were lower in the two cigarette smoke-inhaling groups than in the non-smoking restrained control group, with the lowest values in the high-nicotine/tar group. The plasma levels (8 and 12 h after administration) in the high-nicotine/tar group when theophylline was administered i.p. (10 mg kg-1), were also slightly lower than in the non-smoking restrained control group but this was not significant. When theophylline was administered i.v. (5 mg kg-1), there was no difference between the high-nicotine/tar group and the non-smoking restrained control group. These data indicate that cigarette smoke inhalation causes suppression or delay of theophylline absorption from the gastrointestinal tract.

Administration, Oral

Treatment of complicated urinary tract infections with ofloxacin following an aminoglycoside.

In order to reduce the dosage of aminoglycoside in the treatment of patients with complicated urinary tract infections (UTI) in outpatient clinics and to improve cost benefits, we tried both ofloxacin (OFX) treatment and a combination treatment with OFX and a single dose of aminoglycoside (isepamicin). Both groups showed the same cure rate on day 5, but the bacteriuria elimination rate on day 1 was slightly higher in the isepamicin-OFX group. The recurrence rate on days 7-14 did not differ between the groups. This aminoglycoside-OFX treatment did not show significantly higher effectiveness against complicated UTI but resulted in earlier elimination of bacteriuria. These results suggest that this combination therapy may be cost effective in treating complicated UTI, because of the shorter treatment period required.

Administration, Oral

Influences of cigarette smoke inhalation on pharmacokinetics of cimetidine in rats.

The influences of cigarette smoke inhalation on the pharmacokinetics of cimetidine administered orally and parenterally were investigated in rats using a smoking machine. The animals were exposed to two kinds of cigarette smoke, low- or high-nicotine.tar, inhaled for 10 min immediately after oral (50 mg/kg), intraperitoneal (25 mg/kg) or intravenous (10 mg/kg) administration of cimetidine. The plasma level after cimetidine was administered orally was lower in the absorption phase in the two cigarette smoke inhaling groups than in the non-smoking control group, and was particularly marked in the high-nicotine.tar cigarette smoke inhaling group. In contrast, no significant difference was found in cimetidine plasma level between the cigarette smoke inhaling groups and the non-smoking control group when administered intraperitoneally or intravenously. These results suggest that cigarette smoke inhalation may cause a suppression or a delay in cimetidine absorption from the gastrointestinal tract, and that the degree of influence is dependent upon the content of nicotine.tar in the cigarette smoke.

Administration, Oral

[Clinical analysis of patients with occupational urothelial tumors].

The incidence of occupational urothelial tumor and the accompanied problems were studied on the workers who had manufactured or handled aromatic amines at a certain chemical factory. Twenty-five out of 398 dyestuff workers, who were examined at regular intervals, were found to have urothelial tumors and the incidence rate was 63%. The mean age at onset, the mean period of aromatic exposure and the mean latent period from the initial exposure until tumor development were 61 year-old, 7.2 years and 30 years, respectively. A high incidence rate was found in the long exposed workers and the smoking group. The negative correlation was observed between the age of first exposure to carcinogens and the latent period. The workers who had been exposed to two or three kinds of aromatic amines had the highest incidence followed by those exposed to benzidine and those to alpha-naphthylamine. No urothelial tumor occurred in the workers exposed to beta-naphthylamine. Ninety-four percent of the initial tumors were superficial and transurethral resection of tumors was performed as the initial surgery for the patients with bladder tumors. The recurrence rate in the bladder cavity after the surgery was 39%, which was almost the same rate as that of non-occupational bladder tumors, however, the recurrence rate in the upper urinary tract was high (26%). The positive rate in the examination of urine cytology was 60% for initial tumors, 74% for recurrent tumors. The urine cytology was a significant method for the detection and monitoring of the patients with occupational urothelial tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Naphthylamine

[Treatment of seventy-eight patients with testicular tumors].

Seventy-eight patients with testicular tumors were treated in our clinic between April, 1972 and October, 1990. The average age of patients with seminoma (37.5 yrs) was higher than that (24.5 yrs) of those with non-seminomatous germ cell tumor (NSGCT). Histopathologically, 34 patients had seminoma and 36 patients had NSGCT. The remaining 8 patients had non-germinal cell tumors. The 5-year survival rate was 76.7%, 90.3% and 75.8% for all patients, seminoma group and NSGCT group, respectively. As for seminoma group, the 5-year survival rate was 100%, 50.0% and 33.3% for Stage I, Stage IIb and Stage III, respectively. The survival rate of Stage IIb and Stage III in seminoma group were lower than Stage I statistically. In NSGCT group, the 5-year survival rate was 100% for Stage I and 26.7% for Stage III, between the two groups there was significant difference. The higher serum LDH and HCG levels, the lower the survival rate in NSGCT. Serum AFP, beta-HCG levels and ESR were unrelated to the survival rate. The survival rate for the patients treated by the chemotherapy including CDDP was compared to those treated by the other therapy in germ cell tumor (greater than or equal to Stage IIb). The survival rate of CDDP group was higher than the others (p less than 0.01).

Adult