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Biomedical subjects

J Kawada

Publications and source records attributed to J Kawada.

At least 73 records · Page 4Linked to original sources
PubMed1987

Protective effect of 4,6-O-ethylidene glucose against the cytotoxicity of streptozotocin in pancreatic beta cells in vivo: indirect evidence for the presence of a glucose transporter in beta cells.

Ethylidene glucose (4,6-O-ethylidene glucose; EG) is known to bind the outer surface of the glucose transporter in the membranes of human erythrocytes and other mammalian cells. If a glucose transport system is present on pancreatic beta cells and recognizes the glucose moiety of streptozotocin (STZ), EG should protect beta cells from the cytotoxicity of STZ when it is administered with STZ. This possibility was examined in in-vivo experiments in rats. When EG and STZ were injected into rats together the animals did not become diabetic, as judged by their blood glucose levels, response in a glucose-tolerance test, and insulin secretion in response to feeding. These results suggest that there is a glucose transporter present in beta cells and also the transport of streptozotocin into beta cells through this system.

Animals↗
PubMed1986

Subacute toxicity of methylmercuric chloride and mercuric chloride on mouse thyroid.

Intoxication effect on mouse thyroid by prolonged administration of either CH3HgCl or HgCl2 was studied. It was found by giving CH3 203HgCl and 203HgCl2 through stomach intubation at either a single or a 30 d treatment that thyroid is a moderately susceptible organ to both mercurials. Animals were given 50, 100 and 150 micrograms/d of either mercurial in drinking water for a month. At the lowest amount of HgCl2, body weight was increased, whereas at the highest dose, there was a transient delay in growth. With lower amounts of CH3HgCl, no change in growth was observed. However, at the highest amount, a severe growth inhibition occurred. The thyroid weight was unaffected by lower amounts, but was significantly reduced by 150 micrograms/d of either mercurial. The 24 h radioiodide uptake in the thyroid, expressed by cpm/mg organ weight, was reduced by lower levels of mercurials. CH3HgCl and HgCl2 suppressed the rate of radioiodide incorporation into the iodothyronine fraction, but not into the iodotyrosine fractions, indicating that mercurials do not interfere with organification of iodide but do inhibit the coupling process. Serum thyroxine (T4) level was affected by mercurials, but serum triiodothyronine (T3) was not. This result suggested that even thyroidal secretion of T4 was inhibited by mercurials, but the peripheral conversion of T4 to T3 may not be affected in the maintenance of an active hormone level.

Animals↗
PubMed1986

New diabetogenic streptozocin analogue, 3-O-methyl-2-([(methylnitrosoamino) carbonyl]amino)-D-glucopyranose. Evidence for a glucose recognition site on pancreatic B-cells.

The nonmetabolizable glucose analogue 3-O-methyl-glucose is known to protect pancreatic B-cells against streptozocin (STZ) when injected with or just before STZ. If 3-O-methyl-glucose and the sugar moiety of STZ compete for a glucose recognition site on B-cells, it seemed likely that 3-O-methyl-2-deoxy-2-( [(methylnitrosoamino)carbonyl]amino)-D-glucopyranose, an analogue of STZ with a 3-O-methyl-glucosyl residue, would cause experimental diabetes. This possibility was tested by synthesis of this analogue (alpha-anomer) and comparison of its diabetogenic activity in Wistar rats with that of STZ. Results showed that the compound was diabetogenic and as potent as STZ. This new analogue is the first of the various STZ derivatives reported to show diabetogenic activity. Its activity supports the idea that 3-O-methyl-glucose and STZ bind competitively with a glucose recognition site on pancreatic B-cells.

3-O-Methylglucose↗
PubMed1985

Manganese ion as a goitrogen in the female mouse.

Effect of excessive ingestion of manganese (Mn) on the mouse thyroid was assessed under the conditions of normal intake of iodide. Female mouse thyroids were enlarged after 7 weeks of administration of 200 mg/l MnCl2 X 4H2O in drinking water; 2.74 +/- 0.25 mg for control (N = 56), and 3.31 +/- 0.28 mg for Mn-treated group (N = 85) (p less than 0.001). In contrast, male mouse thyroids never became goitrous following this treatment. Manganese was goitrogenic to the castrated male mouse, but it had no effect on the testosterone-treated castrated male mouse, indicating the involvement of androgen in goiter formation. Oral administration of Mn did not severely affect blocked T/S of 125I or iodine metabolism in the thyroid. A morphological study, however, revealed that the epithelial cell in the Mn-treated mouse thyroid became flatter than that of the control. The lumens were filed with colloid in Mn-treated female mouse thyroid. The serum levels of thyroxine (T4), but not triiodothyronine (T3), were slightly reduced by Mn. These informations suggest that Mn can be a mild goitrogen for the female mouse and that the etiology of goiter formation can be interpreted by retention of colloid in the lumen.

Animals↗
PubMed1983

An ecto-ATPase of thyroidal cell membrane.

The isolated cells were obtained from hog thyroid glands treated with dispase. More than 95% of the cells obtained were intact and viable immediately after preparation, and the cell viability did not change during incubation in the experimental conditions. ATP added to the external medium of whole cell suspensions was hydrolyzed in the presence of various divalent cations, especially Mg, and the rate of hydrolysis of ATP was not significantly different between the Mg-ion system and the completed ion system (Mg+Na+K). When whole cell suspensions were disrupted with homogenizer, the hydrolysis of ATP was markedly increased by adding Na plus K. But there was no difference in the Mg-ion system between cell homogenates and whole cell suspensions. ADP, AMP and adenosine as reaction products were found in the reaction mixture which resulted from the hydrolysis of ATP by whole cell suspensions. Our data suggest that Mg-ATPase in the thyroidal isolated cells is an ectoenzyme whose active site(s) are exposed to the external surface of plasma membrane, and that ATP is finally hydrolyzed to adenosine via ADP and AMP by the enzyme(s).

Adenosine Triphosphatases↗
PubMed1982

The presence of a high concentration of thyroxine in thyroid epithelial cells.

Swine thyroid epithelial cells were isolated and the intracellular concentration of thyroxine was measured by radioimmunoassay and high pressure liquid chromatography. The estimated concentrations of intracellular thyroxine were 1.89 X 10(-8) micrograms/cell by radioimmunoassay, and 0.708 X 10(-8) micrograms/cell by high pressure liquid chromatography, which were equivalent to 4.39 X 10(-5) M and 1.78 X 10(-5) M, respectively. These levels were about a thousand-fold higher than that in the circulation (3.18 +/- 0.59 microgram/dl, 3.98 X 10(-8) M).

Animals↗
PubMed1982

Thyroid xanthine oxidase and its role in thyroid iodine metabolism in the rat: difference between effects of allopurinol and tungstate.

The role of xanthine oxidase in thyroid function was studied in the rat in vivo by different approaches. Allopurinol, an inhibitor of xanthine oxidase, was administered by mixing it with a powdered diet (16 mg/100 g body wt per day for 10 days). This treatment significantly reduced the total uptake of iodide and inhibited the organification of iodide in the rat thyroid gland. Thyroid xanthine oxidase and dehydrogenase were almost completely inactivated by tungstate, which was given to rats (100 p.p.m./animal per day in drinking water for 10 days) maintained on a purified diet containing low levels of molybdenum. Under these conditions, no inhibitory effect was observed on synthesis of thyroid hormones. It therefore seemed reasonable to assume that the suppressive effect of allopurinol on the biosynthesis of thyroid hormones is not mediated by xanthine oxidase.

Allopurinol↗
PubMed1981

No reduction of blood glucose in diabetic rats after oral administration of insulin liposomes prepared under acidic conditions.

Insulin liposomes (dipalmitoyl phosphatidylcholine or dimyristoyl phosphatidylcholine/cholesterol = 7/2) were prepared under strongly acidic conditions maintaining the biological activity of insulin. Although these were apparently noncharged liposomes, the association of insulin with membrane of liposomes was unexpectedly very large, and the uptake % of insulin was high. The distribution of vesicle-size of liposomes was narrow; the average diameter was 9.1 micrometer and no multilayered structures were observed by electron microscopy. Oral administration of the insulin liposomes (15-30 IU/rat) in streptozotocin-diabetic rats did not result in any distinct tendency to reduce the level of blood glucose.

Acids↗
PubMed1980

Effects of organic and inorganic mercurials on thyroidal functions.

Acute effects of methylmercuric chloride and mercuric chloride on thyroidal functions were examined. The organic mercurial concentration of 4 x 10(-5) M inhibited by 50% of Na+K+ATPase in the membraneous preparation from the hog thyroid, and 6 x 10(-7) M of the inorganic mercurial showed the same extent of the inhibition. The Mg2+ ATPase activity in the preparation was neither affected by CH3HgCl up to a concentration of 2 x 10(-3) M, nor by HgCl2 up to 1 x 10(-4) M. After an intraperitoneal injection to mice of 5 micrograms of mercurial per gram body weight daily for 2 consecutive days, the 4-hour and the 24-hour uptakes of 131I by the thyroids were partially reduced by both organic and inorganic mercurials. A significant reduction in percentages of labeled iodothyronines was demonstrated to suggest that mercurial may cause a coupling defect in the synthesis of iodothyronines. Incubation of hog thyroglobulin with 8 x 10(-3) M of methylmercuric chloride caused no observable aberration in slab disc electrophoreogram, but the protein was apparently denatured by the same concentration of mercuric chloride suggesting that thyroglobulin may carry a large binding capacity against either mercurial, but the inorganic mercurial can be more potent denaturant of the protein. The in vitro lysosomal hydrolysis of the mercurial-pretreated rat thyroglobulin which was labeled with 125I in vivo and fortified with the carrier hog thyroglobulin was not affected, but the direct addition of either mercurial in the medium resulted in a significant inhibition of the proteolytic action. Iodotyrosine deiodinase in the thyroid was inhibited by both mercurials in in vitro and in vivo systems. A partial reduction in the serum bound 131I-iodide in both mercurial treated groups was observed at 4 hours and 24 hours after the radioiodide administration. The blood thyroxine levels estimated by radioimmunoassay were quite reduced in the inorganic mercurial treated group and also moderately reduced in the methylmercurial treated group, indicating that the hormone secretion was affected by mercurials.

Adenosine Triphosphatases↗
PubMed1979

Effects of oral administration of positively charged insulin liposomes on alloxan diabetic rats: preliminary study.

Insulin encapsulated in liposomes of various lipid compositions were prepared. The amount of insulin trapped in these liposomes increased in the order, negatively charged liposomes less than neutral liposomes less than positively charged liposomes. In positively charged liposomes, the amount of insulin trapped increased with increase in the amount of amphiphile stearylamine. Under the conditions tested, the highest insulin content (about 50%) was obtained with liposomes composed of phosphatidyl choline/cholesterol/stearylamine in a molar ratio of 7/2/2.25. These liposomes were stable on incubation for 3 hr at 37 degrees C in solutions of pepsin, trypsin, and pancreatin, and after these incubations, a considerable amount of insulin was still associated with the liposomes. However, the liposomes released almost all the insulin into the medium on treatment with bile. When the liposomes were administered orally to rats in the 3rd phase of acute alloxan diabetes, reduction of the blood glucose level was observed in 7 of 11 animals, the reduction persisted for several hours and was ranging from 30 to 75%. In alloxan diabetic rats showing hyperglycemia for 3 to 6 months, the liposomes also increased the glucose tolerance in half the animals tested.

Administration, Oral↗
PubMed1979

Some properties of hog thyroidal membrane-bound adenosine tri-phosphatase: proteolytic activation of Mg-dependent activity.

The ATPase preparations from the hog thyroid was preincubated with various amounts of trypsin. The activity of Mg-ATPase was consistently elevated. On the contrary, the Na, K-ATPase activity decreased with increasing amounts of trypsin. The effects were similar to those which were observed in the enzyme preparations treated with basis polyamino acids as previously reported. This phenomenon seemed to be specific in the preparations from the thyroid. The Mg-dependent activity was increased after pretreatment with trypsin or poly-L-lysine (PLL) when CTP, ITP and UTP were used as substrate. Thus the substrate specificity of Mg-ATPase was low. The enzyme-kinetics using ATP as substrate showed that the increase in activity was due to an increase in Vmax and not to a change in Km. The activity of Mg-ATPase was increased even after 30 min of preincubation with trypsin, while the Na, K-ATPase activity was almost diminished. These results suggest that the activity of Mg-ATPase in the preparation from the thyroid is specifically changed by the modification of the molecular environment of the enzyme with trypsin or basic polyamino acids.

Adenosine Triphosphatases↗
PubMed1976

Further study of the mechanism of thyroid hormone secretion in an in vitro model system: direct evidence for fusion of lysosomes with thyroglobulin liposomes.

The interaction between thyroglobulin liposomes, as a model of colloid droplets, and thyroidal lysosomes was studied in an in vitro system. On sucrose density gradient centrifugation analysis, particulate lysosomes were distributed in a high density region and were apparently clearly separated from the liposomal peak. However, when the liposomes and lysosomes were incubated together and then analyzed, the liposomes were found to migrate with the lysosomal peak. The extent of this translocation of liposomes depended on the incubation temperature: after incubations at 37 C and 0 C, 56% and 35%, respectively, of the radioactivity of liposomes was found in the lysosomal peak. This phenomenon was inhibited by 50% in the presence of 10(-3)M chlorpromazine. Matrix-labeled liposomes [125I]thyroglobulin liposomes), and membrane labeled lipolomes ([14C]-cholesterol-labeled thyroglobulin liposomes) showed similar distribution patterns in the lysosomal peak on gradient centrifugation. The liposomal thyroglobulin was hydrolyzed in a time-dependent manner in the fraction showing both radioactivity and acid phosphatase activity. These results provide direct evidence of liposome-lysosome fusion, or formation of phagolysosomes.

Animals↗
PubMed1976

Some properties of thyroidal membrane adenosinetriphosphatase and iodide uptake: effects of basic polyamino acids.

Poly L-lysine, poly L-ornithine, and histone significantly inhibited the iodide uptake by the thyroid slices, as previously reported. These basic polymers diminshed Na, K-ATPase and concomitantly markedly elevated Mg-ATPase activity in the NaI-treated microsomal preparation and the plasma membrane fraction obtained from thyroid. Poly L-glutamic acid, which was noneffetive to the iodide uptake in vitro, did not show such phenomenon. K-dependent p-nitrophenylphosphatase activity which is considered to reflect the terminal step of the reaction sequence of Na, K-ATPase was also inhibited by poly L-lysine. The effects mentioned above of poly L-lysine and other basic polyamino acids on membrane ATPase system were only found in the preparations from thyroid. The inhibitory effect of these reagents on thyroidal iodide uptake was discussed in terms of the change in membrane ATPase activities.

Adenosine Triphosphatases↗