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Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 163 records · Page 9Linked to original sources

Corneal endothelial cell damage associated with intraocular gas tamponade during pars plana vitrectomy.

A prospective study was conducted of corneal endothelial damage associated with intraocular gas tamponade during pars plana vitrectomy performed in 44 patients. In addition to vitrectomy or combined vitrectomy-lensectomy, 25 patients (the gas-treated group) underwent intraocular gas tamponade, which was not performed in 19 patients (the control group). The central corneal endothelium was examined with a specular microscope preoperatively and 3 months postoperatively. Endothelial changes were quantitated by computerized morphometric analysis of individual cells. A total of 20 eyes were phakic after vitrectomy, 13 eyes in the gas-treated group and 7 eyes in the control group. The mean endothelial cell loss for the gas-treated group (1.9%) did not differ significantly from that for the control group (1.8%). Twenty-four eyes were aphakic after vitrectomy, 12 eyes in the gas-treated group and 12 eyes in the control group. The gas-treated group had a significantly greater cell loss (28.3%) than those in the control group (16.3%).

Air

Biochemical mode of cytotoxic action of neplanocin A in L1210 leukemic cells.

Neplanocin A, a novel antitumor antibiotic, was investigated to determine the biochemical mode(s) of its cytotoxic action. The molecule is an adenosine analogue with a unique cyclopentane structure in its ribose moiety. Both sublines of L1210 and P388 leukemia resistant to neplanocin A were cross-resistant in vitro to bredinin and 9-beta-D-arabinofuranosyladenine, which have been reported to be activated by adenosine kinase. The adenosine kinase activity was markedly reduced in the resistant sublines as compared with that of the respective sensitive lines. Furthermore, neplanocin A competitively inhibited the phosphorylation reaction of adenosine in a cell-free system. The results indicate that neplanocin A is activated by adenosine kinase. Regarding the target site for neplanocin A, the antibiotic suppressed RNA synthesis to a significantly greater extent than DNA synthesis. This RNA-preferential effect is unique among common antimetabolic antitumor agents.

Adenosine

Stability of [3H]ouabain binding to the (Na+ + K+)-ATPase solubilized with C12E8.

The (Na+ + K+)-ATPase from dog kidney and partially purified membranes from HK dog erythrocytes were labeled with [3H]ouabain, solubilized with C12E8 and analyzed by HPLC through a TSK-GEL G3000SW column in the presence of C12E8, Mg2+, HPO4(2-) and glycerol at 20-23 degrees C. The peaks of [3H]ouabain bound to the enzyme from dog kidney and HK dog erythrocyte membranes corresponded to each other with apparent molecular weights of 470 000-490 000. In addition, these bindings of [3H]ouabain to the (Na+ + K+)-ATPase were observed to be stable at 20-23 degrees C for at least 18 h after the solubilization.

Animals

(Na,K)-ATPase and Ouabain binding in reticulocytes from dogs with high K and low K erythrocytes and their changes during maturation.

The present study demonstrated that dog reticulocytes had considerable amounts of (Na,K)-ATPase, but lost it rapidly during maturation into erythrocytes. Furthermore, reticulocytes from dogs possessing erythrocytes characterized with high (Na,K)-ATPase activity and high K, low Na concentrations (HK dogs; Maede, Y., Inaba, M., and Taniguchi, N. (1983) Blood 61,493-499) had more ouabain binding sites than cells from normal dogs (LK dogs). Our results were as follows: i) The maximal binding capacities (Bmax) for ouabain binding at equilibrium were approximately 0 and 1,500 binding sites/cell in LK and HK dog erythrocytes, respectively. ii) Reticulocytes from LK dogs possess approximately 5,700 ouabain binding sites/cell. iii) The Bmax value for ouabain in HK reticulocytes was about 10,000 sites/cell, being 2-fold that in LK reticulocytes. iv) Ouabain-sensitive fluxes of 24Na and 42K in each type of reticulocyte were compatible with the number of ouabain binding sites on the cells. v) Ouabain binding capacity, as well as (Na,K)-ATPase activity, in the reticulocytes from LK dogs fell rapidly to nearly zero during the maturation into erythrocytes. vi) Although reticulocytes from HK dogs also showed a similar regression of (Na,K)-ATPase during maturation, they retained a certain number of ouabain binding sites even after maturation, resulting in the high activity of (Na,K)-ATPase in HK erythrocyte membrane.

Animals

Regional specular microscopy of endothelial cell loss after intracapsular cataract extraction: a preliminary report.

In a group of 10 patients (12 eyes) undergoing intracapsular cataract extraction, corneal endothelial cell loss was serially investigated by means of regional specular microscopy. Prevoperatively there were no significant regional differences in the endothelial cell density. Two weeks after surgery, the superior endothelium alone showed a significant cell loss (15.6%). Whereas, a definite endothelial cell loss occurred in each region of the cornea one month after surgery. The cell loss was greater in the superior (22.8%) and lower in the inferior (4.7%), respectively, when compared to that seen in the central cornea (9.6%). In each region, cell loss continued 3 months postsoperatively, but no significant cell loss occurred thereafter. These results suggest that the entire endothelial cell population may participate in the healing of the damage associated with intracapsular cataract extraction and that regional specular microscopy can be of help for detailed evaluation of such a damage.

Aged

[Antitumor activities of orally administered 4-carbamoylimidazolium-5-olate (SM-108)].

We investigated the antitumor effect of orally administered SM-108. The drug showed strong antitumor activities against Ehrlich carcinoma, sarcoma 180, P388 leukemia, L1210 leukemia, colon 26 adenocarcinoma, colon 38 adenocarcinoma, and Lewis lung carcinoma. The antitumor activity of SM-108 against Ehrlich carcinoma was so remarkable, in fact, that all mice in a group survived for a long time. The antitumor effect of SM-108 depends on its administration schedule. Treatment involving a schedule of one dose every 6 h for 24 h at intervals of 3 days brought about a much stronger effect than daily single treatment. The maintenance of a high serum level of SM-108 for 24 h by the former treatment is responsible for the strong therapeutic effects, because the action of SM-108 is time-dependent. The antitumor activities of SM-108 administered orally are excellent enough to be comparable with those obtained by intraperitoneal administration as previously reported.

Administration, Oral

Occurrence of protein kinases NI and NII in human and porcine thyroids.

Cyclic nucleotide-independent protein kinases that preferentially phosphorylated casein and phosvitin as substrate were detected in the nuclei of human and porcine thyroid tissues, and compared with those from rat liver. Enzymes were extracted from the isolated nuclei with a buffer solution containing 0.4 M NaCl, and analyzed by DEAE-Sephadex and phosphocellulose column chromatographies. The chromatographies, together with the characterization of the enzymes, demonstrated that human and porcine thyroid tissues contained two major casein kinases in the cell nuclei, the properties of which revealed that they are to be identified as protein kinases NI and NII.

Animals

Increase of Na+ gradient-dependent L-glutamate and L-aspartate transport in high K+ dog erythrocytes associated with high activity of (Na+, K+)-ATPase.

As reported previously, some dogs possess red cells characterized by low Na+, high K+ concentrations, and high activity of (Na+, K+)-ATPase, although normal dog red cells contain low K+, high Na+, and lack (Na+, K+)-ATPase. Furthermore, these red cells show increased activities of L-glutamate and L-aspartate transport, resulting in high accumulations of such amino acids in their cells. The present study demonstrated: (i) Na+ gradient-dependent L-glutamate and L-aspartate transport in the high K+ and low K+ red cells were dominated by a saturable component obeying Michaelis-Menten kinetics. Although no difference of the Km values was observed between the high K+ and low K+ cells, the Vmax values for both amino acids' transport in the high K+ cells were about three times those of low ones. (ii) L- and D-aspartate, but not D-glutamate, competitively inhibited L-glutamate transport in both types of the cells. (iii) Ouabain decreased the uptake of the amino acids in the high K+ dog red cells, whereas it was not effective on those in the low K+ cells. (iv) The ATP-treated high K+ cells [(K+]i not equal to [K+]o, [Na+]i greater than [Na+]o) showed a marked decrease of both amino acids' uptake rate, which was almost the same as that of the low K+ cells. (v) Valinomycin stimulated the amino acids' transport in both of the high K+ and the ATP-treated low K+ cells [( K+]i greater than [K+]o, [Na+]o), suggesting that the transport system of L-glutamate and L-aspartate in both types of the cells might be electrogenic. These results indicate that the increased transport activity in the high K+ dog red cells was a secondary consequence of the Na+ concentration gradient created by (Na+, K+)-ATPase.

Animals

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