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Biomedical subjects

Y Inui

Publications and source records attributed to Y Inui.

At least 37 records · Page 2Linked to original sources

Selective increase in cytochrome P450 content in hepatic microsomes from rats with ventromedial hypothalamic lesions.

Changes in the components of hepatic microsomal electron transport systems and in drug hydroxylase activities were investigated in ventromedial hypothalamus (VMH) lesioned obese rats. Eight weeks after electrolysis of the bilateral VMH, the content of cytochrome P450 per mg microsomal protein (0.79 +/- 0.07 nmol/mg protein) was significantly higher (P less than 0.02) than that in the sham-operated rats (0.59 +/- 0.02). Cytochrome P450 per whole liver in the VMH-lesioned obese rats had also significantly increased (87 +/- 9 nmol vs 56 +/- 3, P less than 0.02). No significant differences were found in the cytochrome b5 contents, and the activities of NADPH- and NADH-cytochrome c reductases between the VMH-lesioned obese and sham-operated rats. The demethylation activities of aminopyrine (1.04 +/- 0.02 nmol/mg protein/min vs 0.94 +/- 0.02, P less than 0.05) and p-nitroanisole (0.96 +/- 0.02 vs 0.89 +/- 0.02 , p less than 0.02) and the aniline hydroxylase activity (0.22 +/- 0.01 vs 0.16 +/- 0.01, P less than 0.01) were enhanced, but 7-ethoxycoumarin O-deethylase activity was unchanged in the VMH-lesioned obese rats. These results indicate a selective increase in the content of cytochrome P450 among the components of the P450-dependent mixed function oxidase system in the liver of VMH-lesioned obese rats. Our observations suggest that drug metabolism may be enhanced in the hypothalamic obesity.

Animals

Cortisol enhances the stimulating action of thyroid hormones on dorsal fin-ray resorption of flounder larvae in vitro.

Effects of thyroid hormones and cortisol on fin-ray resorption of the larval flounder were studied in vitro. Dorsal fin rays were dissected from the prometamorphic larvae of the Japanese flounder (Paralichthys olivaceus) and were cultured for 7-8 days in a medium supplemented with different concentrations of thyroxine (T4) or triiodothyronine (T3) or combinations of either thyroid hormone or cortisol (0.1 micrograms/ml). Both T4 and T3 induced shortening of the second fin ray. T3 was more potent than T4; doses of 0.1 and 1.0 micrograms/ml T4 significantly accelerated shortening of the fin rays, whereas T3 was effective at concentrations ranging from 0.001 to 1.0 micrograms/ml. Cortisol further enhanced the effects of both T4 and T3 but was ineffective in the absence of thyroid hormones. When the prometamorphic larvae were reared in water containing T4 (0.01 micrograms/ml), T4 + cortisol (0.10 micrograms/ml), or cortisol alone for 15 days, both the T4- and T4 + cortisol-treated groups showed an advancement of the morphological changes associated with metamorphosis relative to the control group without hormone treatment. However, no clear synergistic effect of cortisol was observed in the in vivo experiment; a sufficient quantity of cortisol may be produced by the larval interrenal.

Animals

Effects of recombinant eel growth hormone on the uptake of [35S]sulfate by ceratobranchial cartilages of the Japanese eel, Anguilla japonica.

Effects of growth hormone (GH) on the synthesis of mucopolysaccharide by ceratobranchial cartilages of the Japanese eel, Anguilla japonica, were examined by monitoring the in vitro uptake of [35S]sulfate. The [35S]sulfate uptake decreased rapidly to one-third of the initial level during the first 3 days after hypophysectomy, and decreased gradually thereafter. When hypophysectomized eels were injected intramuscularly with recombinant eel GH (2 micrograms/g), the plasma GH concentrations increased maximally after 6 hr, and declined rapidly thereafter. On the other hand, the sulfate uptake increased significantly after 12 hr, and high levels were maintained until 48 hr. The stimulating effect of GH was dose dependent (0.02-2 micrograms/g). However, the addition of eel GH (0.05-5 micrograms/ml) to the culture medium did not affect the sulfate uptake by hypophysectomized eel cartilages, suggesting that the stimulative action of GH on the sulfate uptake by the cartilages is indirect.

Anguilla

Evidences for the presence of a somatomedin-like plasma factor(s) in the Japanese eel, Anguilla japonica.

The indirect action of growth hormone (GH) through a somatomedin-like plasma factor(s) on the synthesis of mucopolysaccharides in the ceratobranchial cartilages of the Japanese eel, Anguilla japonica, was studied by monitoring the uptake of [35S]sulfate in vitro. Addition of plasma obtained from intact eels significantly stimulated the sulfate uptake by the cartilages of hypophysectomized eel, whereas plasma from hypophysectomized eels had no effect. On the other hand, the plasma from hypophysectomized eels which had been injected with eel GH significantly stimulated the uptake. The maximal stimulating activity was found in the plasma 24 hr after a single injection of eel GH (2 micrograms/g). This stimulatory activity was dependent on the dose of GH injected. These findings indicate that GH elicits its effect on the cartilages indirectly through a GH-dependent plasma factor(s). The system established in the present study can provide as a biological assay for the somatomedin-like plasma factor(s).

Anguilla

Inhibitory effect of a new alpha-glucosidase inhibitor on fatty liver in Zucker fatty rats.

The livers of Zucker fatty (fa/fa) and lean (Fa/-) rats treated with standard rat chow diet containing 0, 10 or 50 ppm alpha-glucosidase inhibitor (AO-128) for 10 weeks were studied morphologically and biochemically. Light microscopic examination of livers from untreated Zucker fatty rats showed severe steatosis. The triglyceride content in the livers from Zucker fatty rats was significantly higher than that from lean rats (73 +/- 9 micrograms/mg protein for Zucker fatty rats vs. 30 +/- 10 for lean rats, p less than 0.01). Administration of the inhibitor caused a marked decrease in the number and size of lipid droplets in the hepatocytes from Zucker fatty rats and a decrease in the triglyceride content in the liver (73 +/- 9 micrograms/mg protein for untreated, 54 +/- 16 for 10-ppm-treated and 48 +/- 23 for 50-ppm-treated rats, p less than 0.05). This is the first report showing an inhibitory effect of an alpha-glucosidase inhibitor on steatosis in Zucker fatty rats.

Animals

Laparoscopic findings of fatty liver using multiple regression analysis. "Spotty" and "diffuse" yellow color.

Laparoscopic features of fatty liver including the cases with fibrotic change were studied by multiple regression analysis. The coloration of the liver surface under laparoscopy was classified into three types: "spotty" yellow color (YC) type, "diffuse" YC type, and without YC type. The presence of YC on the liver surface depended on the amount of deposited lipid (standardized estimate = 0.606, p = 0.0001). However, the presence of YC and whether it appeared "spotty" or "diffuse" was independent of the intralobular distribution and size of the deposited lipid droplets. When YC was observed in cases without fibrotic change, 19 of the 23 with more than 30% lipid droplets in the biopsy specimens had "spotty" YC. When YC was found in cases with fibrotic change, all of the 14 cases with more than 30% lipid droplets were "diffuse" YC. A linear regression model showed that the yellow colored liver with fibrotic change had a "diffuse" appearance (yes = 1, no = 0) standardized estimate = 0.569, p = 0.0009). These data suggested that the amount of lipid deposited was responsible for the presence of YC on the liver surface both with and without fibrotic change, and that the co-existence of fibrotic change was a major factor for giving the yellow colored liver a "diffuse" appearance.

Biopsy

Increased level of apolipoprotein B mRNA in the liver of ventromedial hypothalamus lesioned obese rats.

The mRNA level of apolipoprotein B (apoB), which is a principal protein component of nascent very low density lipoprotein (VLDL), was determined in parallel with the measurement of acetyl-coenzyme A (Ac-CoA) carboxylase activity in the liver of ventromedial hypothalamus (VMH) lesioned obese rats. Eight weeks after the electrolysis of the bilateral VMH, the level of apoB mRNA in the VMH-lesioned rats was about 1.5-fold higher than that in the sham-operated rats, indicating increased apoB synthesis in the liver of the VMH-lesioned obese rats. The activity of Ac-CoA carboxylase, which is a rate-limiting enzyme for the fatty acid biosynthesis, was about 1.8-fold higher in the VMH-lesioned rats. These observations indicated that VLDL synthesis is increased in the liver of VMH-lesioned obese rats.

Actins

Effects of bovine TSH on the tissue thyroxine level and metamorphosis in prometamorphic flounder larvae.

Bovine thyroid-stimulating hormone (TSH) was microinjected (0.2 microliter/fish) into prometamorphic flounder larvae and the effects on metamorphosis as well as the tissue thyroxine (T4) and triiodothyronine (T3) levels were studied. After a single injection of TSH (5 mIU/g), the tissue T4 concentration increased markedly after 5 hr, reached a peak after 10 hr, and decreased subsequently. T4 concentration after 24 hr was still higher than in saline-injected fish but returned to the control level 48 hr after the injection. On the other hand, tissue T3 concentration was kept lower than the detectable level (0.2 ng/g) throughout the experimental period of 72 hr after a single injection of TSH (5 mIU/g). TSH treatment also accelerated the process of metamorphic climax, such as shortening of the second fin ray and eye migration. These results suggest that an increased secretion of TSH from the pituitary stimulates the thyroid, resulting in a surge of the tissue T4 concentration which induces the climax of the flounder larvae.

Aging

Metabolic improvements associated with a reduction of abdominal visceral fat caused by a new alpha-glucosidase inhibitor, AO-128, in Zucker fatty rats.

The relationship between mesenteric fat accumulation and metabolic disorder was studied in genetically obese Zucker fatty rats. These animals had high levels of plasma glucose, triglyceride and total cholesterol as well as increased liver triglyceride in comparison with lean rats. In addition, portal free fatty acid (FFA) levels were also higher in fatty rats than in lean rats. Direct measurement of fat weight revealed a substantial increase of mesenteric as well as subcutaneous fat. The volume of mesenteric fat cells was greater than that of subcutaneous fat cells in Zucker fatty rats (1.67 +/- 0.49 nl versus 1.00 +/- 0.31 nl), although the mesenteric fat cell volume was less than half of the subcutaneous fat cell volume (0.05 +/- 0.02 nl versus 0.14 +/- 0.07 nl) in lean rats. An increase in mesenteric fat cell volume was thus more predominant than that of subcutaneous fat cells in the fatty rats. Administration of AO-128 (50 p.p.m./day), a new alpha-glucosidase inhibitor, caused a substantial reduction of mesenteric fat weight accompanied by a marked decrease in fat cell volume in Zucker fatty rats. The drug also caused a significant reduction of FFA levels in the portal vein in parallel with a marked reduction of triglyceride content in the liver. These observations indicate that the fat accumulation in the markedly enlarged mesenteric fat cells is related to the elevated levels of FFA in the portal vein, which in turn may cause metabolic disorders in the liver. A new alpha-glucosidase inhibitor improves these disorders, at least in part, by preventing an enlargement of mesenteric fat cells.

Adipose Tissue

Thyroxine surge in metamorphosing flounder larvae.

The tissue concentration of thyroxine (T4) in larval flounder (Paralichthys olivaceus) was studied at various stages of their metamorphosis using a specific radioimmunoassay developed for samples obtained by quantitative extraction of the hormone from fish eggs and larvae. T4 concentrations were below the limit of detection in extracts of fertilized eggs and larvae until the end of prometamorphosis. Several dorsal fin rays continued growing from premetamorphosis until the end of prometamorphosis. The hormone became detectable at the onset of metamorphic climax when the elongated dorsal fin rays stopped growing. A sharp increase in tissue T4 concentration was observed in midclimax of metamorphosis, and the high level of T4 (11-13 ng/g body weight) was maintained until the end of the climax. The period of elevated T4 levels coincided with resorption of the elongated dorsal fin rays. The right eye completed translocation from the right to the left side of the body during metamorphic climax. The tissue T4 level declined to about a half of the peak value during postclimax, and then increased moderately in later adult-type juveniles. The results of an additional experiment, in which fertilized eggs and newly hatched larvae were treated with T4 and/or thiourea, suggested the presence of negative feedback regulation of pituitary-thyroid axis, implying an involvement of thyroid hormones even in early premetamorphic larvae. These results suggest that metamorphic climax is induced by a surge of thyroid hormone, and that thyroid hormone may also regulate development before and after the metamorphosis.

Animals

Effects of various doses of thyroxine and triiodothyronine on the metamorphosis of flounder (Paralichthys olivaceus).

Two experiments were carried out to clarify the effects of thyroxine (T4) and triiodothyronine (T3) on flounder metamorphosis. In the first experiment, three doses of T4 were administered to premetamorphic flounder larvae together with thiourea (TU). Thiourea treatment (30 ppm in ambient seawater) alone caused metamorphic stasis in the fish, although the beginning of the right eye migration was not completely inhibited. T4 at 100 and 10 ppb in ambient seawater induced metamorphosis in the thiourea-treated larvae. The fish of these groups completed translocation of the right eye to the left side and resorption of elongated dorsal fin rays. However, 1 ppb T4 failed to induce metamorphic climax. The elongated dorsal fin rays continued to grow until the end of the experiment in the group treated with TU alone and in combination with 1 ppb T4. In the second experiment, premetamorphic flounder larvae were treated with two doses of T4 and three doses of T3. The T3 treatment was several times more potent than T4 treatment in the induction of metamorphosis. The results of the present study suggest that the metamorphic events of flounder larvae are dependent on the thyroid hormone concentration, and the relative biological potency of T4 and T3 on flounder metamorphosis is similar to that observed in mammals and amphibia.

Animals

[A case of hepatocellular carcinoma with bone metastasis which responded to oral administration of UFT].

A 61-year-old male was referred to our hospital for evaluation of right upper arm pain. He was diagnosed as having primary hepatocellular carcinoma with bone metastasis by his high titer (111,683 ng/ml) of serum alpha-fetoprotein, computed tomography and abdominal angiography, and so UFT therapy, 400 mg daily, was instituted. After 2 months of this therapy, the titer of serum alpha-fetoprotein gradually decreased. Seven months later, the titer was 3,997 ng/ml and reduction of the hepatic tumor size was shown by computed tomography and ultrasonography. Furthermore, the right upper arm pain diminished and X-ray examination revealed remarkable improvement. During chemotherapy, there was no severe side effect apart from mild anemia and the patient is presently still alive. This case suggests the efficacy of UFT for the treatment of primary hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols

Morphological study of lipoprotein particles in the livers of ventromedial hypothalamus lesioned rats.

Ultrastructure of the liver in ventromedial hypothalamus (VMH) lesioned rats was studied in parallel with biochemical examination. Ten weeks after the operation, VMH lesioned rats became markedly obese. Electron microscopic examination of the liver revealed lipid droplets in the cytoplasm and a high load of lipoprotein particles in the Golgi elements. Lipoprotein particles, 40-50 nm in diameter, in the Golgi elements, were scattered throughout the cytoplasm. Concentrations of triglyceride and esterified cholesterol markedly increased in the liver, while those of free cholesterol and phospholipids did not increase. Serum concentrations of triglyceride, total cholesterol and HDL-cholesterol in VMH lesioned rats were higher than control ones. These data suggest that lipoprotein synthesis was markedly increased in the livers of VMH lesioned rats.

Animals

Molecular basis of a unique tumor antigen of radiation leukemia virus-induced leukemia B6RV2: its relation to MuLV gp70 of xenotropic class.

Hybridomas secreting monoclonal antibodies that reacted with the B6 radiation leukemia virus (RadLV)-induced leukemia B6RV2 were produced by fusion of BALB/c NS-1 myeloma cells with spleen cells from (BALB/c X B6)F1 mice immunized with B6RV2. By direct and absorption analyses with 28 B6 and BALB/c leukemias, the monoclonal antibodies NU7-4 and NU7-99 were shown to react only with B6RV2, indicating that they recognized an individually distinct antigen on B6RV2 that was identified previously with conventional (BALB/c X B6)F1 anti-B6RV2 serum. Another monoclonal antibody, NU1-132, showed relatively restricted reactivity with B6 RadLV leukemias. These three monoclonal antibodies all precipitated material of approximately 80,000 daltons, which is the same size as that precipitated by anti-xenotropic MuLV gp70 serum. Sequential immunoprecipitation analysis revealed that the molecules precipitated by NU7-4 were not removed by pretreatment of NU7-99 or NU1-132 and that the molecules precipitated by NU7-99 were not removed by NU7-4 or NU1-132. The molecules precipitated by NU1-132 were partially removed by pretreatment with NU7-4, but not with NU7-99. The molecules precipitated by these three monoclonal antibodies were removed by pretreatment with anti-xenotropic gp70. These results suggested heterogeneity of the xenotropic MuLV gp70-related molecules expressed on B6RV2 and a possible relation between serologically defined unique tumor antigens and gp70-related molecules.

Animals

Effects of the intravenous administration of magnesium sulfate on corrected serum calcium level and nephrogenous cyclic AMP excretion in normal human subjects.

The effect of intravenous magnesium sulfate infusion on corrected serum calcium level and parathyroid function assessed by determination of nephrogenous cAMP (NcAMP) excretion were studied in normal human subjects. Significant hypermagnesemia induced by the magnesium sulfate infusion for 120 minutes was accompanied by a gradual and progressive decrease in the corrected serum calcium level. NcAMP excretion fell rapidly, reaching a nadir between 60 and 120 minutes after the infusion began, and after that rose above the baseline excretion. Urinary calcium excretion gradually increased, reaching a peak between 120 and 180 minutes after the infusion began and then gradually decreased. Since magnesium was given as the sulfate, it is not clear whether these changes were attributable to magnesium or sulfate or both. As a control study, we performed intravenous sodium sulfate infusion. The sodium sulfate infusion caused slight hypocalcemia, slight hypercalciuria, and a significant increase in NcAMP excretion. These findings indicate that the hypocalcemia and the hypercalciuria caused by the magnesium sulfate infusion is mainly due to the effect of magnesium, and that the decrease in NcAMP excretion during the infusion is due to the effect of magnesium alone. We conclude that the hypocalcemia caused by the magnesium sulfate infusion is mainly due to the renal calcium loss, and that the inhibition of parathyroid function caused by hypermagnesemia may be only partially involved in the early phase of this hypocalcemia.

Adult

Thyroid hormone induces metamorphosis of flounder larvae.

The role of thyroid hormone in flounder metamorphosis was studied by use of thyroxine and the antithyroidal agent, thiourea (TU). T4 stimulated metamorphosis of pelagic larvae, producing miniatures of naturally metamorphosed benthic juveniles. In contrast, TU induced metamorphic stasis, resulting in giant pelagic larvae. These results indicate that the thyroid plays a role in flounder metamorphosis comparable to its well-known developmental role in amphibian metamorphosis.

Animals