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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
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

[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↗
PubMed1983

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↗
PubMed1982

Reduction of lethal toxicity of chloroethylnitrosoureas by sugar alcohols without loss of antitumor activity.

Sugar alcohols, such as mannitol, sorbitol, galactitol, and inositol, selectively reduced the acute lethal toxicity of 1-(2-chloroethyl)-3-(methyl alpha-D-glucopyranos-6-yl)-1-nitrosourea (MCNU) without reducing its antitumor activity. Fifty mg MCNU/kg killed all CD2F1 mice within about 10 days, while the administration of 3,000 mg sugar alcohols/kg immediately prior to MCNU protected mice from the lethal toxicity and all survived. The amelioration of MCNU toxicity by sugar alcohols was dose-dependent. Pretreatment with mannitol 1 day before MCNU administration was effective. In addition, a series of five daily treatments with lower doses of mannitol was also effective. This protection was accompanied by the reduction of both body weight loss and myelosuppression. The antitumor effects of MCNU on P388 leukemia and Lewis lung carcinoma were not significantly altered by mannitol treatment. These phenomena were not limited to MCNU, the lethal toxicity of GANU, ACNU, Me-CCNU, and mitomycin C also being reduced by mannitol treatment.

Animals↗
PubMed1982

Characteristic distribution of two forms of chromatin-bound RNA polymerase II in rat liver nuclei.

We have shown that, in rat liver nuclei, the chromatin-bound RNA polymerase II is released as two different forms on digestion with micrococcal nuclease or DNase I (peak 1 and peak 2). To elucidate the origin of the two forms of the enzyme, we examined their distribution in fractionated chromatins obtained by mild micrococcal nuclease digestion of the nuclei. About half of the total peak 2 activity was recovered in a nuclease-sensitive chromatin fraction which contained DNA enriched in the sequences appearing in the polysomal polyadenylated mRNA. On the other hand, four-fifths of the total peak 1 activity was recovered in a nuclease-resistant chromatin fraction which contained DNA comprising only two thirds of the transcribed sequences. Furthermore, during the nuclease digestion, peak 2 activity was rapidly released from the chromatin, whereas peak 1 activity was gradually released. These results indicate that the two forms of RNA polymerase II are distributed differently in the cell nuclei.

Animals↗
PubMed1982

A case report on disequilibrium hypercalcemia in hyperthyroidism. Comparison of calcium metabolism with other patients with hyperthyroidism.

The patient, a 30-year-old woman, was admitted to Itoh Hospital in February, 1979 for hyperthyroidism. She had a history of pyelonephritis and recurrent urinary tract infection. Laboratory data on admission revealed overt hyperthyroidism (T3: 405 ng/dl, T4: 22.5 micrograms/dl and T3U: 57.--%), severe hypercalcemia of 12.6 mg/dl and hypercalciuria. The PSP excretion and GFR were both decreased. Serum c-PTH was nondetectable. As the thyroid function improved, there was a gradual decrease and later normalization of plasma calcium, phosphate and urinary calcium excretion. When subtotal thyroidectomy was performed on October 19, 1979, hypertrophy of the parathyroid gland was not demonstrated. In comparison with 98 other hyperthyroid patients, the pathogenesis of hypercalcemia was discussed. In conclusion, hypercalcemia in the patient, T. Y., was regarded as a kind of disequilibrium hypercalcemia which resulted from a combination of increased bone turnover and decreased calcium excretion by the kidney.

Adult↗
PubMed1982

New antitumor imidazole derivative, 5-carbamoyl-1H-imidazol-4-yl piperonylate, as an inhibitor of purine synthesis and its activation by adenine phosphoribosyltransferase.

The mechanism of action of 5-carbamoyl-1H-imidazol-4-yl piperonylate (SL-1250), which has a broad antitumor spectrum, was examined by in vitro cell culture and enzymatic studies. In the serum-containing culture medium, SL-1250 was rapidly deacylated to 4-carbamoylimidazolium 5-olate (SM-108). Thus, SL-1250 might be acting on the cells in the form of SM-108. The growth of L5178Y cells was completely inhibited by 10(-5) M SL-1250. It should be noted that this growth inhibition was significantly reversed in the presence of equimolar concentrations of guanine, guanosine, or guanosine 5'-monophosphate to those of SL-1250. However, hypoxanthine and xanthine were not effective. These effects of purine addition were observed to be quite similar in growth inhibition by SM-108. It was found that inosine 5'-monophosphate dehydrogenase (EC 1.2.1.14; IMP dehydrogenase), a key enzyme of de novo purine synthesis, from Ehrlich carcinoma cells was inhibited by SM-108 only when 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) and MgCl2 coexisted with SM-108. In contrast, a chemically synthetic ribonucleotide of SM-108 inhibited IMP dehydrogenase without PRPP and MgCl2, and the mode of inhibition was competitive with the Ki value of 2 x 10(-8) M. On the other hand, the inhibition of either growth of L5178Y cells or IMP dehydrogenase in the presence of PRPP and MgCl2 by these compounds was reversed by adenine. A nucleotide of SM-108 was chromatographically identified when [14C]SM-108 was incubated in the enzyme solution with PRPP and MgCl2. This conversion by enzyme was also inhibited by adenine. Viewed together, these results strongly suggest that SL-1250 is, after being converted to SM-108, activated to its nucleotide form by adenine phosphoribosyltransferase (EC 2.4.2.7) and that this SM-108 nucleotide blocks de novo synthesis of guanosine 5'-monophosphate by inhibiting IMP dehydrogenase.

Adenine Phosphoribosyltransferase↗
PubMed1982

Collateral sensitivity of 6-mercaptopurine-resistant sublines of P388 and L1210 leukemia to the new purine antagonists, 5-carbamoyl-1H-imidazol-4-yl piperonylate and 4-carbamoylimidazolium 5-olate.

Two new purine antagonists, 5-carbamoyl-1H-imidazol-4-yl piperonylate (SL-1250) and 4-carbamoylimidazolium 5-olate (SM-108), were investigated for their antitumor activities against 6-mercaptopurine (6-MP)-resistant sublines of P388 and L1210 leukemia. It was found that both resistant sublines exhibited collateral sensitivity instead of cross-resistance to these new antipurine drugs. Since more potent cytotoxic activities of these drugs against 6-MP-resistant cells were observed even in vivo cell culture systems, this collateral sensitivity was proved on a cellular basis. Biochemical studies revealed that 6-MP-resistant sublines of both P388 and L1210 leukemia are deficient in hypoxanthine-guanine phosphoribosyltransferase activity. In these cells, not only the activation of 6-MP to its nucleotide but also the synthesis of guanosine 5'-monophosphate via the salvage pathway seems to be severely restricted. However, SL-1250 and SM-108 can be activated to their nucleotide even in these 6-MP-resistant cells because the activation of these compounds is proceeded by adenine phosphoribosyltransferase. In conclusion, suppression of de novo purine synthesis with SL-1250 and SM-108 seems to be a very efficient means of killing these 6-MP-resistant cells, which lack a salvage pathway for guanosine 5'-monophosphate.

Animals↗
PubMed1982

[General observation on drug resistance of cancer cells].

General discussions on the drug resistance of cancer cells were made from various points of view: (1) drug resistance as an unhereditary phenotype, (2) changes in the cell population during drug treatment, (3) acquired resistance and natural resistance, (4) general concepts on biochemical and pharmacological mechanisms for drug resistance, (5) common mechanism for concurrent resistance to DNA-intercalators and vinca-alkaloids, and (6) collateral sensitivity on a cellular basis.

Animals↗