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Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 91 records · Page 5Linked to original sources
PubMed1990

The effects of lipoxygenase products on progesterone and prostaglandin production by human corpora lutea.

The present study was undertaken to assess the effects of the products of the lipoxygenase pathway on steroidogenesis and the production of prostaglandins (PGs) by human corpora lutea in the midluteal phase. In the first experiment luteal cells were cultured with 5-hydroxyeicosatetraenoic acid (5-HETE) at 10, 100, 500, or 1000 ng/mL in the presence or absence of hCG at 100 ng/mL for 10 days. The addition of 5-HETE dose-dependently inhibited progesterone (P) production by the cultural luteal cells. P production stimulated by exposure to hCG was also reduced significantly in response to 5-HETE. However, 5-HETE had no effect on the production of 6-keto-PGF1 alpha, PGF2 alpha, or PGE2 by cultured luteal cells at any point during the culture period. In the second experiment the reaction products of soybean lipoxidase of arachidonic acid (AA-LIP) were added to cultured luteal cells. Treatment with either AA or LIP alone had no effect on basal P production. The addition of AA-LIP at all concentrations tested reduced P production by cultured luteal cells in the presence or absence of hCG. AA-LIP significantly reduced basal 6-keto-PGF1 alpha secretion in cultured luteal cells on day 2. Although the stimulatory effect of AA on luteal PGE2 production was maintained throughout the entire culture period, the lipoxygenase products of AA did not affect AA-stimulated PGE2 production by cultured luteal cell. These results suggest that the products of the lipoxygenase pathway may be important in the involution of human corpora lutea.

Adult↗
PubMed1990

The effect of the follicular fluid adenosine 3',5'-monophosphate degradation rate on successful fertilization and cleavage of human oocytes.

Follicular fluid (FF) and oocytes were obtained from 19 women for in vitro fertilization. Ovulation was induced with clomiphene citrate and human menopausal gonadotropin. Thirty-seven FF samples containing mature oocyte-corona-cumulus complexes were used to measure steroids, gonadotropins, and cAMP. The FF specimens were divided into three groups: follicles yielding ova that were fertilized and cleaved (group A), follicles containing fertilized ova without further cleavage (group B), and follicles containing nonfertilized oocytes (group C). The FF levels of progesterone, 17 beta-estradiol, LH/hCG, and FSH did not differ significantly among the groups. Mean FF cAMP concentrations declined from 17.5 +/- 2.5 pmol/mL 15 min after follicle aspiration to 3.6 +/- 0.9 pmol/mL after 3 h. The initial FF cAMP concentration did not differ significantly among three groups. However, the cAMP degradation rate in group A (119 +/- 13 X 10(-4) pmol/min) was significantly greater than that in group B (62 +/- 10 X 10(-4) pmol/min) or group C (75 +/- 8 X 10(-4) pmol/min). In conclusion, an increased intrafollicular cAMP degradation rate was associated with successful fertilization and cleavage of human oocytes in vitro. These data suggest that the degradation rate of FF cAMP may be a marker of optimal follicular development and oocyte maturation.

Adult↗
PubMed1990

Allopurinol protects pancreatic beta cells from the cytotoxic effect of streptozotocin: in vitro study.

Isolated rat pancreatic beta cells in monolayer culture were shown to be protected from the cytotoxic effect of streptozotocin (STZ) by allopurinol. Pretreatment with allopurinol for 2 h caused dose-dependent inhibition of the decreased secretion of insulin by the cells induced by STZ (2 mM, for 1 h), 500 microM allopurinol causing complete inhibition of this effect of STZ. Pretreatment with allopurinol (250 microM) also prevented the rapid decrease in intracellular adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide concentrations in beta cells induced by treatment with STZ. High performance liquid chromatography revealed that the intracellular concentration of uric acid in STZ-treated cells was about 3 fold that of control cells. This finding suggests that the reaction of xanthine oxidase is facilitated in the cells exposed to STZ probably due to an increased supply of substrate resulting from decrease in intracellular ATP. Based on these results, a possible mechanism of the effect of allopurinol on the cytotoxic effect of STZ via xanthine oxidase is discussed.

Adenosine Triphosphate↗
PubMed1990

Direct evidence for the presence of methylmercury bound in the thyroid and other organs obtained from mice given methylmercury; differentiation of free and bound methylmercuries in biological materials determined by volatility of methylmercury.

Peroxidase in mouse thyroid was inhibited by mercuric chloride but not by methylmercury in in vivo and in vitro systems (Nishida, et al., J. Histochem. Cytochem., 37, 723 (1989)). To identify the reason for the difference, the present study was conducted to examine whether methylmercury is indeed bound within cells or tissues. Mice were given radioactive methylmercury by intubation for 18 d and the tissues were dissected out and vacuum-dried. With this procedure, free methylmercury was evaporated off and the bound mercury remained. The thyroid, liver, kidney and fats examined showed no loss of radioactivity under the vacuum, indicating that the mercury was bound to the thyroid, as well as the other tissues. Radioactive mercuric chloride was nonvolatile regardless of the presence or absence of the tissues. The preferential affinity of methylmercury for SH-containing materials was re-confirmed by this method.

Animals↗
PubMed1990

Effect of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones on iodide uptake by the mouse thyroid: the relationship between their structure and anti-thyroid activity.

Antithyroid activity of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones was tested by measuring the uptake ratio of thyroid: serum (T/S) of 125I through the mouse thyroid. Substitution with an alkyl group at the 5-position of the triazole nucleus remarkably increased the activity but substitution at the N-2 and/or N-4 positions caused a significant decrease in the activity, indicating the necessity of unsubstituted thioureylene moiety for the antithyroid activity. Thiosemicarbazone derivatives which are an open ring structure of triazoles showed comparable antithyroid activities to those in a ring form, but one thiosemicarbazone showed a much higher toxicity than the corresponding ring form compound. This suggests that the ring structure is not essential for the activity but is necessary to reduce toxic effect. Of fourteen compounds tested, 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione was the most potent antithyroid compound with low toxicity, with a potency tenfold that of propylthiouracil, a drug currently used.

Animals↗
PubMed1990

Importance of the concentration of ATP in rat pancreatic beta cells in the mechanism of streptozotocin-induced cytotoxicity.

The effects of streptozotocin (STZ) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on monolayer cultures of rat pancreatic beta cells were compared. The intracellular NAD concentration was markedly decreased by both 2 mmol STZ/l and 13.6 mumol MNNG/l, but insulin secretion was decreased significantly only by STZ. The intracellular ATP level decreased rapidly and in a time-dependent manner with STZ, but decreased less on treatment with MNNG: 80% decrease with STZ but only 35% decrease with MNNG in 12 h in the cells exposed to the chemicals for 1 h and then washed thoroughly. STZ decreased oxygen consumption of rat liver mitochondria in a time- and dose-dependent manner and enhanced the generation of hydroxyl radicals (DMPO-adducts). This enhancement was doubled on the addition of succinate as a substrate. Mitochondrial ATP production was also decreased significantly by STZ, but not by MNNG. Thus the marked depletion of intracellular ATP in beta cells by STZ seems to be due mainly to a direct effect on mitochondrial production. From these results, we suggest that the cytotoxic effect of STZ in pancreatic beta cells is due to a reduction in the intracellular level of ATP, rather than of NAD.

Adenosine Triphosphate↗
PubMed1990

Isolation, characterization and structures of PA-46101 A and B.

New antibiotics, PA-46101 A and B, were isolated from the culture broth of a Streptomycete. The molecular formulae of A and B were determined to be C52H70O18 and C61H86O22, respectively, by elemental analyses, NMR and mass spectrometry. Their structures were elucidated by X-ray crystallography and NMR spectroscopy. These antibiotics are active in vitro against anaerobic Gram-positive and Gram-negative bacteria and also against a limited number of aerobic Gram-positive bacteria.

Aminoglycosides↗
PubMed1990

Structure of di-O-alpha-maltosyl cyclodextrins produced from alpha-maltosylfluoride and cyclodextrins.

The structures of di-O-alpha-maltosyl beta-cyclodextrins ((G2)2-beta-CDs), which were produced from alpha-maltosylfluoride (alpha-G2F) and cyclodextrin (CD) by the transfer action of debranching enzymes, were examined by the enzymic method using Bacillus subtilis saccharifying alpha-amylase (BSA). (G2)2-beta-CD was converted to (G1)2-beta-CD by treatment with glucoamylase before the examination. BSA completely hydrolyzed (G1)2-beta-CD to produce glucose, 6(3)-O-alpha-glucosylmaltotriose, and 6(3),6(5)-di-O-alpha-glucosyl maltopentaose. (G2)2-beta-CD was the mixture of 6A,6C-di-O-alpha-maltosyl beta-CD and 6A,6D-di-O-alpha-maltosyl beta-CD. The ratio of A,C/A,D in (G2)2-beta-CD synthesized with Pseudomonas isoamylase and Aerobacter pullulanase were 40:60-45:55 and 30:70, respectively. The content of 6A,6C-di-O-alpha-maltosyl gamma-CD in (G2)2-gamma-CD synthesized by isoamylase was about 35%.

Bacillus subtilis↗
PubMed1990

Phosphate and pepsin adsorptions by a new boehmite compound and aluminum hydroxide.

A new microcrystalline compound of aluminum oxide hydroxide (tentatively named PT-A) was synthesized in the hope of providing a better phosphate adsorbent for future clinical use than the currently marketed aluminum hydroxide gels (ALG). An X-ray diffraction study demonstrated a boehmite structure in PT-A but an amorphous structure in ALG. PT-A was more stable in pH change than ALG; in elution tests in artificial gastric and intestinal solutions, aluminum ion eluted from PT-A was maximally 10% of the amount from ALG at pH 1.2; and was undetectable at pH 6.8, at which point ALG still showed some aluminum elution. Phosphate-adsorbing efficacy of PT-A and ALG in vitro was about the same at pH 1.2; however, it was four times greater in PT-A than in ALG at pH 6.8, indicating that PT-A will be effective in the intestine. PT-A also adsorbed pepsin but the amount was at most the same or much less than that adsorbed by ALG, which depended on pH in solution.

Adsorption↗
PubMed1990

[Effects of 5-hydroxyeicosatetraenoic acid (5-HETE) on progesterone and prostaglandin production by human corpora lutea].

The present study was undertaken to assess the effects of 5-hydroxyeicosatetraenoic acid (5-HETE) on steroidogenesis and prostaglandin (PG) production in cultured luteal cells derived from human corpora lutea in the mid-luteal phase. The luteal cells were cultured with 5-HETE at 10, 100, 500, or 1,000 ng/ml in the absence or presence of hCG at 100 ng/ml for 10 days. The addition of 5-HETE to the culture media did not affect growth curves of cultured luteal cells. 5-HETE significantly inhibited progesterone (P) production by cultured luteal cells in a dose-related fashion on day 2. P production stimulated by exposure to hCG was also reduced significantly in response to 5-HETE. The addition of 5-HETE did not affect estradiol production by cultured luteal cells. The production of 6-keto-PGF1 alpha by cultured luteal cells in the presence of 5-HETE was slightly but not significantly less than that observed in the absence of 5-HETE. However, 5-HETE affects neither PGF2 alpha nor PGE2 production by cultured luteal cells throughout the culture period. The present study demonstrates that 5-HETE inhibits P production in cultured luteal cells by a mechanism(s) other than through PG production. These data suggest the involvement of a lipoxygenase pathway in the synthesis of P and 6-keto-PGF1 alpha of luteal cells.

Adult↗
PubMed1990

[Treatment of leiomyomas with luteinizing hormone-releasing hormone agonist].

Twenty-five premenopausal women, 36-54 years of age, with uterine myomas were treated with 600-1,200 micrograms/day of luteinizing hormone-releasing hormone agonist (LHRHa) for 4 months. Eight patients reached menopause following the treatment with LHRHa (menopause group), while the resumption of menstruation occurred within 12 weeks after cessation of the therapy in 17 patients (menstruation group). Although the mean hemoglobin (Hb) concentration in the menopause group increased during treatment and was maintained within the normal range after cessation of the therapy, the Hb concentration in the menstruation group decreased after the resumption of menstruation. Both estradiol and CA125 in the menopause group were reduced during and after treatment. However, these parameters in the menstruation group increased concomitantly with the resumption of ovarian function. LH and FSH were suppressed during treatment, but these gonadotropins in the menopause group increased significantly to the levels of menopause. About a 50% reduction in uterine volume was observed in the menopause group. Three months after completing therapy, the restoration of uterine volume occurred in the menstruation group. Bone density findings in microdensitometry 12 weeks after cessation of the therapy did not differ significantly from those before the treatment. These results demonstrate that LHRHa therapy significantly reduces the uterine volume in patients with leiomyoma. It may be possible to treat selected patients with leiomyoma, including perimenopausal women and high surgical risk women with LHRHa, thus avoiding the need for surgery.

Adult↗
PubMed1990

[A study of combined chemotherapy with MMC, ADM, CDDP, etoposide (VP-16), 5'DFUR (MAC-VD therapy) in advanced cancer and local relapse of the stomach].

Eighteen patients with progressive/locally recurrent cancer of the stomach were given therapy with MMC, ADM, CDDP, Etoposide (VP-16), and 5'DFUR (MAC-VD therapy). Drugs were administered intravenously with MMC 10 mg/m2, ADM 20 mg/m2, and CDDP 50 mg/m2 on day 1; orally with etoposide 100 mg/day for five consecutive days from day 3; and orally with 5'DFUR 600 mg/day for three weeks from day 3 followed by discontinuation for one subsequent week. This drug regimen was one course of the treatment and repeated as far as possible. There were 16 evaluable cases; the sex distribution was ten males and six females. Patients ranged in age from 43 to 78 years. P.S. 1 was two cases; 2 ten cases; and 3 four cases. The overall response rate, CR + PR, was 1 + 7/16 (50%), while this rate for primary disease was 2 + 5/16 (43.8%). Of the two CR cases, one primary lesion became operable and CR was demonstrated histologically. The overall response rates, CR + PR, for metastatic lesions were 1 + 3/9 (44.4%) for the liver; 0 + 1/4 (25.0%) for the abdominal lymph nodes; 0 + 1/2 (50.0%) for the superficial lymph nodes; 0 + 1/2 (50.0%) for the bones; and 0 + 1/1 (100%) for the lung. The median duration of the response was 3.7 months (range between 1.5 and 8.2+) and the median duration of survival 5.1+ months (range between 2.2+ and 13.3+). At the same time, the hematological side effects of both leukocytopenia and hypohemoglobinemia were seen in 43.8% of the cases. Non-hematological side effects included alopecia in 18.8% and nausea/vomiting in 12.5%. There was no case of discontinuation due to side effects. It was concluded that the therapy with MMC, ADM, CDDP, etoposide and 5'DFUR (MAC-VD therapy) proved to be a very promising drug regimen in the treatment of stomach cancer with high rates of response and is expected to be a step forward in the establishment of interdisciplinary treatment.

Administration, Oral↗
PubMed1990

[The changes in tumor markers such as serum CEA, CA 19-9, TPA and CA 125 in the chemotherapy of patients with advanced gastric cancer].

Twenty-five patients with advanced gastric cancer were treated with a combination chemotherapy. The levels of serum CEA, CA 19-9, TPA and CA 125 were measured before and during chemotherapy (4 and 8 weeks). One complete and 10 partial responses were obtained, and the response rate was 44%. Pretreatment positive rates of these four tumor markers were all more than 60%, and the positive rate of combination assay was 96%. The mean percent changes of these four tumor markers were similar and correlated well with the response to chemotherapy. There was a significant correlation between tumor reduction and decrease of serum CEA in the responders with measurable lesions. These results suggest that the measurement of changes of serum tumor markers may be useful for monitoring the response to chemotherapy in patients with gastric cancer. It also may be useful to determine early the effectiveness of the treatment.

Adolescent↗
PubMed1990

Direct evidence for ATP consumption due to iodide uptake by isolated, uncultured, pig thyroid epithelial cells.

The concept that iodide uptake by thyroid requires a supply of ATP is currently accepted. However, there is little direct evidence that the extents of iodide uptake and ATP consumption are correlated. To demonstrate this correlation, we used isolated, uncultured pig thyroid epithelial cells in basal media containing only glucose and the cations necessary for Na+,K(+)-ATPase, which prevented other possible cellular activities requiring ATP. The isolated cells were sensitive to various metabolic inhibitors of ATP-generating systems, confirming that they were intact. The extents of increase in iodide uptake and decrease in ATP content of the cells were entirely dependent on the presence of the cations, and were closely correlated with each other. Furthermore, the ATP content was not reduced in the absence of NaI, even when all necessary cations for the ATPase were present. These findings provide direct evidence for a correlation between the extents of iodide uptake and ATP consumption. Cells in medium with Mg alone did not show iodide incorporation or ATP consumption, confirming that Mg2(+)-dependent ATPase does not contribute to iodide uptake by the thyroid.

Adenosine Triphosphate↗
PubMed1990

Variations in manganese effect on 6-phosphogluconate dehydrogenases from the thyroid and liver of the mouse and an evidence for non-interchangeability of manganese and magnesium.

Both manganese (Mn) and magnesium (Mg) are known to activate 6-phosphogluconate dehydrogenase (6-PGDH). Yet in the present study none of the metal ions stimulated 6-PGDH from the thyroid of mice, but Mn alone stimulated the enzyme from the liver. Such a stimulatory effect of Mn on the liver enzyme was seen regardless of the presence of Mg, This suggests that the reaction sites for the two ions must be apart from one another or that the affinity of Mn is stronger than that of Mg. The enzyme preparations from livers of those mice which had been administered intraperitoneally with excess of Mn for 1 - 14 days were greatly stimulated by further in vitro addition of Mn, whereas the enzyme sources from the thyroids thus treated were almost insensitive to Mn in vitro. The results indicate that cellular Mn hardly reaches the levels for maximal stimulation of the enzyme in the liver. In addition, some sex difference was observed in the Mn effect on 6-PGDH from the liver.

Animals↗
PubMed1990

[Possible involvement of leukotriene B4 on human luteal function: special reference to determination of leukotriene B4 produced by cultured luteal cells].

The present study was undertaken to determine the production of leukotriene B4 (LTB4) by cultured human luteal cells in the mid-luteal phase using a reverse phase column (C8). The luteal cells were cultured with or without hCG at 100 ng/ml for 8 days. In the preliminary experiment, methods for extracting culture media samples were assessed prior to radioimmunoassay. Reverse phase column C8, but not C18, made possible the determination of LTB4 produced by human luteal cells. Progesterone (P) production by cultured luteal cells reached its maximum on day 4 following exposure to hCG, and then declined gradually. The concentrations of LTB4 produced by luteal cells varied from 100 to 500 pg/10(5) cells/2 days. However, exposure to hCG did not affect LTB4 production by cultured luteal cells. The level of LTB4 in culture medium (115.0 +/- 37.8 pg/10(5) cells/2 days) was reduced on day 4, but increased thereafter. LTB4 production appeared to decrease concomitantly with increased P production of cultured luteal cells. In conclusion, cultured luteal cells produced considerable amounts of LTB4 throughout the entire culture period. These results suggest that lipoxygenase activity of luteal cells may be closely related to steroidogenic potential.

Adult↗
PubMed1990

Progesterone protects oocytes from premature degeneration within the follicle.

The present study was designed to determine the effects of gestrinone (R2323) in the process of follicle rupture and oocyte maturation and degeneration in an in vitro perfused rabbit ovary model. In the first experiment, R2323 at 10(2), 10(3), or 10(4) ng/ml was added to the perfusate of one ovary. The contralateral control ovary was perfused simultaneously with medium alone. Thirty minutes after the onset of perfusion, 50IU of human chorionic gonadotropin (hCG) was added to the perfusate of both ovaries. All ovaries exposed to R2323 plus hCG or hCG alone ovulated. The addition of R2323 to the perfusate did not affect the ovulatory efficiency of ovaries treated with hCG. No significant difference in the percentage of ovulated ova or follicular oocytes demonstrating germinal vesicle breakdown was seen with R2323 treatment. R2323 increased the degeneration rate of ovulated ova in a dose-dependent fashion. In the second experiment, in which experimental ovaries were perfused with R2323 (10(4) ng/ml) plus progesterone (10(3) ng/ml) and the control ovaries with R2323 (10(4) ng/ml) alone ovulation occurred in response to hCG. However, the addition of progesterone to the perfusate reduced the degeneration-inducing effect of R2323 on both ovulated ova and follicular oocytes. In conclusion, R2323 appears to act as an antiprogesterone, thereby promoting the degeneration of oocytes. The increased production of progesterone in the preovulatory follicle following the gonadotropin surge protects oocytes from premature degeneration within the follicles.

Animals↗