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Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 433 records · Page 24Linked to original sources

Is it necessary to adjust the replacement dose of thyroid hormone to the season in patients with hypothyroidism?

Hypothalamo-pituitary-thyroid activity varies with the temperature of the environment; we therefore measured variables involved with thyroid function in summer and winter in normal controls and in patients with primary hypothyroidism. All seven patients had impalpable thyroid glands and had received a set replacement dose of thyroxine for over a year. In the patients, serum T3 and FT4 levels were slightly but significantly lower in winter, and TSH levels and delta TSH at 30 minutes in the TRH tests were significantly higher. In the controls, there were no significant differences between summer and winter in these values. These findings suggest that the dose required for replacement of thyroid hormone in patients with hypothyroidism may be higher in winter than in summer.

Adult↗

Serum and tissue coenzyme Q9 in rats with thyroid dysfunctions.

Serum and tissue CoQ9 levels were determined in hypothyroid, euthyroid and hyperthyroid rats. A significant negative correlation was demonstrated between serum FT4 or T3 and CoQ9 in rats with various states of thyroid functions. Liver CoQ9 was significantly increased in rats rendered mildly hyperthyroid. There was a significant positive correlation between serum FT4 or T3 and liver CoQ9. While liver CoQ9 did not significantly change in severely hyperthyroid animals, liver mitochondrial CoQ9 showed a significant positive correlation with serum T3. Kidney and heart CoQ9 levels did not significantly change in hyperthyroid rats, but those in hypothyroid rats showed a tendency to increase. It was suggested that the synthesis of CoQ9 was increased in the liver in hyperthyroidism.

Animals↗

Two species of chromatin-RNA polymerase II complex are commonly present in nuclei of various tissues of rats.

When rat liver nuclei were digested with nuclease, we found that the chromatin-bound RNA polymerase II was liberated as two distinct complexes, peak 1 and peak 2, which seemed to reflect different functional states in cell nuclei. We further examined their occurrence in nuclear digests of various tissues of rats and the following results were obtained. Upon digestion with micrococcal nuclease of nuclei from brain, spleen, testis and kidney, chromatin-bound RNA polymerase II was liberated as two distinct forms which sedimented differently in a sucrose density gradient. The sedimentation rate of peak 1 varied depending on the tissue nuclei examined. After high salt or RNase treatment of the nuclear digests, peak 1 from liver, brain, spleen and testis nuclei showed the same sedimentation rate as did kidney peak 1, the rate for which remained unchanged by these treatments. The results suggested that peak 1 complexes from various tissue nuclei had basically the same structural organization, and we confirmed this by electrophoretic studies on RNase-treated liver and kidney nuclear digests. Peak 2 from various tissue nuclei exhibited identical sedimentation rates. Thus, the chromatin-bound RNA polymerase II seems to exist commonly in two distinct states in cell nuclei of rats.

Animals↗

Increased micrococcal nuclease sensitivity and/or solubility in nuclei from Graves' disease thyroid tissue.

The sensitivity of nuclei to micrococcal nuclease was compared in thyroid tissue obtained from euthyroid patients with solitary cold nodules and from patients with Graves' disease. A significant increase in the solubility and/or the sensitivity of nuclei to the nuclease was found in thyroid tissue from patients with Graves' disease. Electrophoretic analysis of DNA in chromatin solubilized by the nuclease revealed that the amount of oligonucleosomal DNA was increased, and that of polynucleosomal DNA was even more increased, in nuclei from Graves' thyroids than in those from normal thyroids. Polyacrylamide gel electrophoretic analysis in Triton acid-urea showed that the extent of histone acetylation in nuclei from Graves' thyroids was almost the same as in those from normal thyroids. These findings suggest that the state of chromatin organization in Graves' thyroid nuclei is different from that in normal thyroid nuclei and is independent of the extent of histone acetylation.

Acetylation↗

Tissue calmodulin levels in normal and Graves' thyroids.

Calmodulin levels in normal human thyroids and Graves' disease thyroids were measured by specific radioimmunoassay in the presence of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The calmodulin levels in tissues from patients with Graves' disease treated with thionamide drugs were significantly higher than those in normal tissues from euthyroid patients with solitary cold nodules (normal: 484 +/- 50 ng/mg protein, mean +/- SE, n = 15; Graves': 901 +/- 54 ng/mg protein, n = 48, p less than 0.001). Such a rise in calmodulin levels in Graves' disease thyroids was also present even after the administration of 50 micrograms of T3 for 5 days before operation (828 +/- 137 ng/mg protein, n = 6, p less than 0.01). Calmodulin levels in Graves' disease thyroids were closely related to the cell height of follicular epithelium. Calmodulin levels in a columnar cell predominant group were significantly higher than those in a flat cell predominant or a cuboidal cell predominant group (columnar cell predominant: 1150 +/- 118 ng/mg protein, n = 13; flat cell predominant: 561 +/- 125 ng/mg protein, n = 3, p less than 0.05; cuboidal cell predominant: 596 +/- 40 ng/mg protein, n = 25, p less than 0.001). The increase in calmodulin content in Graves' disease thyroid could therefore possibly be attributed to the stimulation of the thyroid gland by the thyroid stimulating antibody. An immunofluorescence study demonstrated the presence of calmodulin immunoreactivity in the thyroid epithelial cells, particularly enriched in the apical border in the form of a granulated structure.

Calmodulin↗

Cross-resistance of vincristine-resistant sublines of P388 leukemia to mitoxantrone with special emphasis on the relationship between in vitro and in vivo cross-resistance.

In vitro and in vivo cross-resistance to mitoxantrone of two vincristine-resistant sublines of P388 leukemia with different degrees of resistance in vitro was compared with that to adriamycin. A subline with a lower degree of resistance to vincristine exhibited approximately the same responses in vivo to mitoxantrone and adriamycin as the original P388 leukemic cell line, although it was evidently cross-resistant in vitro to these agents. Another subline having a higher degree of resistance to vincristine showed a 25-fold cross-resistance in vitro and gave no response in vivo to adriamycin. With mitoxantrone, on the other hand, this subline was solidly resistant as compared with the sensitive line but still retained significant responsiveness in vivo irrespective of a 150-fold cross-resistance in vitro. These results suggest that cross-resistance on a cellular basis does not necessarily correspond to in vivo cross-resistance. The relationship between in vitro and in vivo cross-resistance is discussed.

Animals↗

Light microscopic and electron microscopic study on morphologic features resulting in the delay of ICG elimination in diabetic and non-diabetic fatty liver.

Disturbances of intravenously administered indocyanin green (ICG) elimination are related to the effective circulating blood volume and the amount of binding protein for transportation in blood plasma through the liver because of the narrowed sinusoidal space due to the enlarged liver cells with fullness of confluent fat droplets in the cytoplasma. However, morphologic changes of the liver resulting in disturbances of ICG elimination could not be actually clarified until the present. Therefore, morphologic changes of the liver resulting in delayed ICG elimination in fatty liver, occurring in diabetes mellitus were investigated in contrast with those in fatty liver in non-diabetic, non-alcoholic diseases of the liver. An electron microscopic study of the liver with delayed ICG elimination revealed thickening and amorphous growth of the sinusoidal wall with obscure pores followed by membraneous formation, narrowness of Disse's space, rarefaction of sinusoidal microvilli and proliferation of collagen fibers, in fatty livers derived from both diabetes mellitus and other diseases. The term "intrasinusoidal block" in fatty liver should be utilized on the basis of these electron microscopic features of the liver.

Adult↗

Reversal of multidrug resistance by non-antitumor anthracycline analogs.

It was found that three synthetic anthracycline analogs lacking not only antitumor activity but also calcium-antagonizing action possessed an activity to potentiate vincristine cytotoxicity against vincristine-resistant P388 leukemia. ID-8279, one of these analogs, significantly reversed resistance to vincristine and daunorubicin by increasing their intracellular accumulation.

Animals↗

Corporal punishment in schools: myths, problems and alternatives.

In many countries, corporal punishment of school children continues to be an officially or unofficially sanctioned form of institutional child abuse. Continuing support for the use of corporal punishment is related to the following factors: (1) widely held beliefs regarding the effectiveness of corporal punishment, (2) an unawareness of problems resulting from the use of physical punishment, and (3) a lack of knowledge about effective disciplinary alternatives. The purpose of this paper is threefold: One is to show that many of the beliefs are myths, e.g., corporal punishment is not needed to build character. The second purpose is to show that physical punishment can lead to more problems than it appears to solve, e.g., the punitive teacher is avoided, and thus, is not a positive factor in the child's education and development. The third purpose is to discuss two types of alternatives to punishment, the social learning approach and communication skills training. These positive methods of discipline not only enhance classroom behavior, but also facilitate learning. In an atmosphere free of abusing and demeaning acts and in a classroom characterized by positive mutual regard, teachers can maximize their effectiveness as teachers and students can maximize their effectiveness as learners.

Behavior Therapy↗

Increase of Na-K-ATPase activity, glutamate, and aspartate uptake in dog erythrocytes associated with hereditary high accumulation of GSH, glutamate, glutamine, and aspartate.

We have found convincing evidence for the presence of Na-K-ATPase and high potassium (K) and low sodium (Na) concentrations in the erythrocytes of some dogs associated with hereditary high concentrations of erythrocyte glutathione and some amino acids, glutamate, glutamine, and aspartate. The Na-K-ATPase activity of the erythrocyte membranes of the dogs was about 3 times that of human erythrocyte membranes, whereas the enzyme activity was not detected in control dogs with a normal level of blood glutathione. The Michaelis constant of the enzyme for ATP (Km ATP) was 6.6 X 10(-3)M in the dogs' erythrocytes and 5.0 X 10(-4)M in the human erythrocytes. The concentration of K in the erythrocytes in the dogs examined was about 11 times that of the controls, whereas the erythrocyte Na concentration in the dogs was about one-third that of the controls. The concentrations of K and Na in the plasma of the dogs were equal to those of the controls. Furthermore, L-3H-glutamate and L-3H-aspartate uptake by those cells with high activity of Na-K-ATPase greatly increased, while L-3H-glutamine uptake was unchanged. It appeared that Na+ and K+ gradients created by Na-K-ATPase across the cell membrane might stimulate glutamate and aspartate uptake by the cells, thus causing the high accumulation of such amino acids in the cells.

Amino Acid Metabolism, Inborn Errors↗

[Experimental study on the evaluation of antineoplastic effects in the human cancer/nude mouse system].

Human tumor/nude mouse system is expected to be an antitumor screening system with higher predictability of the clinical effect. To establish this, it is quite necessary to fundamentally investigate the optimal treatment regimen in this new model, nevertheless few papers related to these subjects are currently, available. In this preliminary report, we examined the effect of several known antitumor agents against human breast tumor xenograft, MX-1, with reference to the dose, route and schedule of administration of drugs in comparison with the clinical regimens. As a result, the treatment regimens were desirable to be similar to that clinically done: the route of administration should be IV or PO, instead of IP often used in usual animal experiments. The selection of dose would be the most important factor, that is, the maximum tolerated doses (MTD) of mitomycin C, vincristine, etc. were higher than the clinical doses, even in terms of dose per square meter. Thus, for these drugs the risk to overestimate the effect might exist. On the other hand, the case was opposite as for 5-fluorouracil, because its MTD in the nude mouse was lower than the clinical dose. To evaluate the effect of a drug, it appeared to be reasonable to make account of not only the average percentage of tumor growth inhibition but also the statistical means such as Mann-Whitney's U-test.

Adenocarcinoma↗

Optimal treatment schedule and antitumor spectrum of 4-carbamoylimidazolium 5-olate (SM-108) in murine tumors.

By designing optimal administration schedules, it was found that 4-carbamoylimidazolium 5-olate (SM-108) showed an excellent antitumor potency against a number of murine tumors. The optimal administration schedule of SM-108 was an intermittent multiple administration, in which the drug was multiply administered to mice at definite intervals of less than 3 hr for about 1 day on Days 1, 5, and 9 following tumor implantation. Although usual daily administration of SM-108 exhibited poor efficacy, the intermittent multiple administration of SM-108 exhibited potent antitumor activity against a wide variety of tumors, such as Ehrlich carcinoma, P388, 6-mercaptopurine-sensitive and -resistant L1210, Lewis lung carcinoma, Colon 26 adenocarcinoma, and Sarcoma 180. Among them, Ehrlich carcinoma showed the most prominent susceptibility to SM-108. With the intermittent multiple administration of SM-108, complete suppression was obtained in both the ascitic and solid forms of this tumor over a wide dose range. The schedule dependency of the antitumor effect of SM-108 described above was reasonably explained by its in vitro growth-inhibitory effects and pharmacokinetics in the mice.

Animals↗