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Biomedical subjects

T Karube

Publications and source records attributed to T Karube.

At least 19 recordsLinked to original sources

[The effect of beta-adrenergic blockade on the plasma potassium elevation induced by acute respiratory acidosis during halothane or fentanyl anesthesia].

The effect of beta-adrenergic blockade on the plasma potassium elevation induced by acute respiratory acidosis (CO2 inhalation) was studied in adult mongrel dogs during halothane or fentanyl anesthesia. Twenty-two dogs were divided into 4 groups: halothane-control (HC, n = 15), halothane-beta-blockade (H beta, n = 8), fentanyl-control (FC, n = 15) and fentanyl-beta-blockade (F beta, n = 10). Beta-blockade was achieved by continuous infusion of propranolol. The maximum levels of plasma potassium after 14% CO2 inhalation were 5.0 +/- 0.7 mM (mean +/- SD) in HC, 6.1 +/- 0.8 mM in H beta, 4.3 +/- 0.4 mM in FC and 4.8 +/- 0.5 mM in F beta. With halothane anesthesia more prominent elevation was observed in the beta-blockade group (P < 0.05), but with fentanyl anesthesia this elevation was not significantly different between the two groups. In acute respiratory acidosis, pH-induced plasma potassium elevation is suppressed by simultaneously increased catecholamines, especially epinephrine. Beta-adrenergic blockade, therefore, may cause severe hyperkalemia due to inhibition of adrenergic potassium disposal. During fentanyl anesthesia plasma potassium elevation was less marked than during halothane. This indicates that fentanyl has less suppressing action on the secretion of stress hormones, including epinephrine, under similarly stressful conditions as halothane anesthesia.

Acidosis, Respiratory↗

Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung-cancer patients.

For further study of the correlation of L-myc restriction-fragment-length polymorphism (RFLP) and metastasis of lung cancer to lymph nodes or other organs at the time of surgery, L-myc RFLP was analyzed in 252 Japanese lung-cancer patients. A close correlation between L-myc RFLP and metastasis was confirmed in this large number of patients (p = 0.01). The correlation was particularly pronounced in cases of adenocarcinoma and squamous-cell carcinoma. Poor prognosis (additional metastases after surgery) was observed in lung-cancer patients with L-S (identified as long and short bands produced with EcoRI) and S-S type L-myc RFLP. In addition, the death rate of lung-cancer patients with the L-S and S-S types was greater than that of those with the L-L type. Lung-cancer patients of the L-S and S-S types had almost 4 times higher incidence of multiple cancer in the lung, pharynx and other organs than those with the L-L type. Our results indicate that, in patients with lung cancer, genetic disposition with respect to the L-myc gene influences the extent of metastasis, the incidence of multiple cancers and prognosis.

Combined Modality Therapy↗

Modification of the clastogenic activity of X-ray and 6-mercaptopurine in mice by prefeeding with vitamins C and E.

The effect of a 30-d pretreatment with vitamin C (L-ascorbic acid) in the drinking water and vitamin E (all-rac-alpha-tocopherol) in the diet on the clastogenic activity induced by X-rays and 6-mercaptopurine was investigated in female ICR/Jcl mice by the bone-marrow micronucleus test. Prefeeding with vitamin E-deficient diets led to a significant decrease in serum vitamin E concentration and to an enhancement of micronucleus formation by X-rays in bone marrow cells. Although dietary supplementation with vitamin E significantly increased the vitamin E concentration in serum, it did not affect the frequency of X-ray-induced micronuclei. Treatment with a high level of vitamin C in drinking water was effective in protecting against micronucleus formation by X-rays. The increase in micronucleus frequency in the vitamin E-deficient mice compared with the mice fed vitamin E-normal diets was no longer observed when a high level of vitamin C in drinking water was given simultaneously. The most efficient protective action against X-rays was observed when vitamin E-supplemented diets and a high level of vitamin C in drinking water were used together as a pretreatment. Any combination of the vitamins did not affect the micronucleus induction by 6-mercaptopurine.

Animals↗

[Synthesis and benzodiazepine receptor binding studies of pyridazino[3,4-b]indoles].

A series of methyl 9H-pyridazino[3,4-b]indole-3-carboxylates and related compounds were synthesized using a Diels-Alder reaction of methyl 3-(1H-indol-3-yl)-2-propenoates and dibenzyl azodicarboxylate. Several compounds were found to have high affinity for the benzodiazepine receptor. Their structure-activity relationships are discussed.

Animals↗

Changes of common fragile sites on chromosomes according to the menstrual cycle.

The frequencies of chromosomal breaks and sister chromatid exchanges (SCE) are influenced by pregnancy, oral hormonal contraceptives and the menstrual cycle. The changes in the number and sites of spontaneous and aphidicolin-induced breaks on chromosomes from peripheral blood lymphocytes during the menstrual cycle were examined in 8 healthy women. Menstrual cycle was determined by menstruation and the quantity of serum estrogen, progesterone and luteinizing hormone. The number of spontaneous breaks at the follicular phase, the interval phase (which includes ovulation) and the luteal phase were 3.1 +/- 1.1, 2.7 +/- 2.3 and 3.9 +/- 2.6 per 100 mitoses, respectively. The frequencies of aphidicolin-induced breaks in the same phases were 95.8 +/- 23.3, 90.6 +/- 14.3 and 122.7 +/- 20.1 per 100 mitoses, respectively. The higher frequency at the luteal phase was statistically significant compared with the other phases. In the luteal phase, bands 2q32, 3q27, 6q26 and 16q23 had higher frequencies of breaks (P less than 0.05); however, breaks at band 9q32 decreased significantly. SCE showed considerable variation, but with no statistical significance.

Adult↗

Promoting effect of sodium chloride solution mist on the induction of papillomas on Syrian hamster tracheal mucosa following administration of diethylnitrosamine.

The promoting effect of NaCl solution mist was studied in the induction of papillomas on Syrian hamster trachea following single subcutaneous injection of diethylnitrosamine (DEN). Sixty male hamsters were divided into three groups. Group A; Exposure to a 5% NaCl solution mist for 32 weeks following single subcutaneous injection of DEN at a dose of 3 mg/100 g body weight. Group B; Subcutaneous DEN injection alone. Group C; Exposure to the NaCl mist for 32 weeks alone. Total numbers of papillomas on the trachea in each group were 107 in group A, 64 in group B, and 0 in group C (P less than 0.05 between group A and B, P less than 0.01 between either groups A or B and C). Comparing the incidence of large papillomas with a diameter of more than 2 mm, that in group A hamsters was significantly greater than that of group B (22 large papillomas vs. 8 large papillomas, P less than 0.01). No difference in the effects on the epithelial cells of the nasal cavity, the bronchial or the alveolar cells in the lung was recognized between groups A and B. The hamsters in group C were not observed to have any changes in any of the respiratory organs. Inhalation of NaCl solution mist is considered to have a promoting effect on the induction of papillomas in the hamster trachea following DEN injection.

Adenocarcinoma↗

[Cytogenetic analyses of diesel engine exhaust by sister chromatid exchange and micronucleus tests with mouse fetal liver cells].

The genotoxic effect of maternal exposure to diesel engine exhaust was studied by analyses of sister chromatid exchanges (SCEs) and formation of micronuclei with fetal liver cells. Fetal liver cells were obtained from pregnant ICR/JCl mice at the 16th day of gestation. Diesel engine exhaust was generated by running a small engine (YANMAR NSA-40CE, used as an electric generator, displacement: 269 cc). The concentrations of pollutants in the inhalation chamber were as follows; CO: 40-100 ppm, NO2: 2-4 ppm, and particulates: 2-4 mg/m3. Maternal mice were divided into three groups: the long-term exposure group, the short-term exposure group and the non-exposed control. Mice of the long-term group were exposed to the exhaust 4 hours daily from day 0 to the 16th day of gestation. Mice of the short-term group were similarly exposed but only on the 15th and 16th days of gestation. The number of SCEs of fetal liver cells was significantly increased in both the exposed groups. The long-term exposure group showed a significant increase in the number of SCEs in comparison with that of the short-term exposure group. In the micronucleus test with fetal liver cells, no significant change in the frequency of micronucleated cells was induced by exposure to diesel exhaust.

Animals↗

Effects of midazolam on the threshold of lidocaine-induced seizures in the dog--comparison with diazepam.

The anticonvulsive effect of midazolam was compared with that of diazepam in ten dogs. Lidocaine-induced seizure waves on the electroencephalogram were used to observe the suppressive effect of the drugs. Midazolam, 0.2 mg.kg(-1), was found to possess a stronger suppressive effect against lidocaine-induced seizures than the same dose of diazepam. These two drugs showed to possess similar effects on cerebral and systemic circulations and cerebral metabolism during seizures.

Journal Article↗

Analyses of transplacentally induced sister chromatid exchanges and micronuclei in mouse fetal liver cells following maternal exposure to cigarette smoke.

The effect of maternal exposure to cigarette smoke on the fetus was studied by analyses of sister chromatid exchange (SCE) and formation of micronuclei with fetal liver cells. Fetal tissues were obtained from pregnant ICR/Jcl mice at the 16th day of gestation. Mice were exposed to mainstream or sidestream cigarette smoke with or without passage through filter (gas phase smoke or whole smoke). Each stream of smoke was used for three exposure schedules, i.e., short-term (two exposures at 15th and 16th day of gestation), long-term (exposure started at 4 wk before mating and stopped at 16th day of gestation), and prepregnant term (exposed for 4 wk before mating). The number of SCEs of fetal liver cells was significantly increased in all exposed groups. In the mainstream experiments, the long-term group showed a significant increase in the number of SCEs in comparison with that in the short-term group. Exposure to sidestream smoke increased the number of SCEs more than in groups exposed to mainstream smoke. This tendency was also recognized in the experiments with filtered smoke. On the contrary, no significant changes were observed by the micronucleus test. The transplacental genotoxic effect of maternally inhaled cigarette smoke was accurately detected by analysis of SCEs with fetal liver cells.

Animals↗

Induction of squamous metaplasia, dysplasia and carcinoma in situ of the mouse tracheal mucosa by inhalation of sodium chloride mist following subcutaneous injection of 4-nitroquinoline 1-oxide.

Squamous metaplasia, dysplasia and carcinoma in situ (CIS) were induced in the ICR/Jcl mouse tracheal mucosa by exposure to a mist of 5% NaCl solution following single subcutaneous injection of 4-nitroquinoline 1-oxide (4-NQO). Either subcutaneous injection of 4-NQO or NaCl inhalation alone did not cause any marked change in the tracheal mucosa. The NaCl inhalation is considered to have promotion-like action on the mouse tracheal mucosa after administration of 4-NQO injection.

4-Nitroquinoline-1-oxide↗

Comparative studies of the effects of RS-8359 and safrazine on monoamine oxidase in-vitro and in-vivo in mouse brain.

The effect of RS-8359, pyrimidine on monoamine oxidase (MAO) has been compared with a hydrazinic MAO inhibitor, safrazine (beta-piperonylisopropylhydrazine hydrochloride,) which is a MAO inhibitor used clinically. In-vitro radiochemical determination of MAO activity showed that the IC50 of RS-8359 was 0.52 microM for the deamination of 5-hydroxytryptamine (5-HT) in the mouse brain mitochondrial preparation, while beta-phenylethylamine (PEA) deamination was inhibited by only 20% at 100 microM of the drug. 5-HT deamination in the brain homogenate prepared from mice killed 60 min after administration of RS-8359 was inhibited significantly by 14 and 48%, at 30 and 100 mg kg-1 (p.o.), respectively, while deamination of PEA was little affected at the same doses. On the other hand, safrazine strongly inhibited both 5-HT and PEA deaminations, but showed no selectivity toward the substrate used. The extent of MAO inhibition by RS-8359, measured fluorometrically with kynuramine as a substrate in the brain homogenate, was independent of preincubation up to 80 min. In contrast, the inhibitory potency of safrazine was strengthened by preincubation in a time-dependent manner. Oral administration of RS-8359 (3-30 mg kg-1) caused a dose-dependent increase in endogenous monoamines in mouse brain, which disappeared a few hours after its administration. Increase in monoamine content caused by safrazine lasted for at least 24 h. These results indicate that RS-8359 is a reversible and specific inhibitor of MAO-A, while safrazine is an irreversible and non-specific MAO inhibitor, in-vivo and in-vitro in mouse brain.

Animals↗

Analysis of the chromosomal DNA replication pattern using the bromodeoxyuridine labeling method.

The DNA replication of human lymphocytes was studied using the labeling pattern on chromosomes after pulse labeling with bromodeoxyuridine and immunostaining with the monoclonal antibody to bromodeoxyuridine. The sites of bromodeoxyuridine incorporation were defined by comparison with the same karyotype treated G-banding, and a more precise analysis was performed using the image analyzer, Maziscan III. Early phase DNA synthesis roughly coincided with R-bands and late phase DNA synthesis with G-bands. One case of acute myeloid leukemia which developed from myelodysplastic syndrome, had a 46,XY, t(4;11) (p12;p15) karyotype, and revealed an altered DNA replication time at the translocated site, 4p15, from the late to the early phase. The present method was useful in detecting an alteration of DNA replication timing according to chromosomal translocation.

Bromodeoxyuridine↗

Studies on the assessment of neurotoxicity in children with acute lymphoblastic leukemia.

Central nervous system (CNS) prophylaxis caused a remarkable reduction in the incidence of CNS disease, however there has evolved a growing concern regarding the immediate or late toxicities to the developing CNS. Twenty-eight children with acute lymphoblastic leukemia who survived for more than 2 years were examined for the assessment of neurotoxicity induced by CNS prophylaxis and its treatment. The patients were stratified into three groups: Stratum I, prophylaxis with methotrexate; Stratum II, prophylaxis with cranial irradiation with methotrexate; and Stratum III, with CNS leukemia. Once CNS disease developed the sequelae were frequent and severe, due to the elevated methotrexate levels in the cerebrospinal fluid. CNS prophylaxis with intermediate-dose methotrexate was less toxic to the developing CNS than prophylactic cranial irradiation, especially in children under 5 years of age. Electroencephalograms and evoked potentials are likely to find increasing application in defining the CNS sequelae of acute lymphoblastic leukemia in children and its treatment. Although the sample size was small, the findings delineate specific areas of neurotoxicity.

Adolescent↗

A case of congenital lymphoblastic leukemia: clinical course and significance of ultrasonography.

A case of congenital leukemia in which texture changes in ultrasonography were followed up is reported. The patient was a male infant hospitalized on day 22 after birth with multiple bluish skin nodules. Complete remission was achieved easily, but he relapsed early and died from the disease after six months. Because of L1 morphology the disease was classified as acute lymphoblastic leukemia, but the leukemic cells lacked the characteristics of lymphoid lineage on cytochemical, cytogenetic, immunological, and enzymological examination. Ultrasonography was considered a useful tool in the following respects for the treatment of the patient with congenital leukemia: The texture of the infiltration of leukemic cells into the liver was clearly visualized and changes in the images could be traced both in size and in number; the process of ventricular dilatation and brain atrophy were successively visualized.

Atrophy↗