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Biomedical subjects

R Okamoto

Publications and source records attributed to R Okamoto.

At least 163 records · Page 9Linked to original sources
PubMed1992

Antigonadotropic activity of hop extract.

Biological activity of water soluble fractions F-1 and F-2, which were extracted from hop, was studied and its action mechanism was speculated using the immature female SD rats. Administration of the substance significantly inhibited the effects of pregnant mare serum gonadotropin (PMSG) on 22-day-old female rats. Thus, PMSG-induced increases in ovarian weight, estrogen secretion, number of ovulated egg, progesterone production, uterine thymidine kinase activity, and plasma LH level were suppressed significantly. Furthermore, addition of the substance to incubated ovarian cells of the second day after PMSG injection resulted in suppression of FSH-induced estradiol secretion in vitro, probably via cAMP-dependent mechanism. But addition of the substance to incubated pituitary cells from ovariectomized rats did not change in LH secretion.

Animals↗
PubMed1992

A novel steroidogenic role of suramin-blocked luteal cell growth factors.

Growth factors synthesized in the ovarian corpus luteum (CL) have been implicated in the development of the CL. One of these growth factors is basic fibroblast growth factor which acts on luteal cells in an autocrine manner (Tamura et al. 1991; Asakai et al. 1992). To elucidate effects of these growth factors in the development of the CL, we cultured immature luteal cells with defined medium for a week in the presence or absence of a growth factor inhibitor, and measured progesterone in the medium as an indicator of cell differentiation. Culture of luteal cells showed an increased amount of progesterone for three days and continued to synthesize progesterone for at least another four days without serum and pituitary hormones. The addition of suramin, previously reported to inhibit autocrine growth stimulation, accelerate the daily progesterone production of luteal cells apparently by switching on the early onset of differentiation. Suramin also induced apoptosis of the cells after the 3rd day of culture. These data suggest that an autostimulation mechanism by growth factors plays a physiological role on normal cell differentiation, and it is not limited to neoplastic transformation.

Animals↗
PubMed1992

Thymidine kinase activity in familial adenomatous polyposis.

Thymidine kinase (TK) activity of polyp tissue from patients with familial adenomatous polyposis (FAP) was measured and compared with that of normal colon, sporadic polyp and colorectal carcinoma tissues. Total TK activity in colonic carcinoma was 3-fold that of normal; this increase seems attributable mainly to increased activity of cytosolic TK isozyme activity; the colorectal TK isozymes were separated into two types, i.e., fetal type and adult type isozymes predominantly in, respectively, cytosolic and mitochondrial fractions, by DEAE-cellulose column chromatography. However, FAP polyp samples from 15 patients showed an average elevation of only 1.8-fold over normal. Examined individually, only 5 of the 15 FAP samples showed significant elevations in total TK activity. Furthermore, TK isozyme analysis revealed variable patterns of the cytosolic isozyme activity being elevated in some cases (8 of 15) and remaining low in others. Thus FAP polyps seem to be a heterogenous population with respect to DNA replicative activity, and cytosolic TK isozyme activity may constitute a biochemical marker for the subsequent development of colorectal carcinoma in FAP.

Adenomatous Polyposis Coli↗
PubMed1992

Family of a patient with serum cholinesterase deficiency.

A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E1s indicating familial serum cholinesterase deficiency.

Adult↗
PubMed1992

Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. I. Isolation of antibiotic-blocked mutants and their characterization.

Biosynthetically blocked mutants were obtained from a baumycin-producing Streptomyces sp. D788 newly isolated from soil. The first mutant isolated was a baumycin-negative but daunorubicin-accumulating mutant with a loss of 4'-substitution activity, from which all other blocked mutants were successively derived. These included a known 11-deoxydaunorubicin-producing mutant and several new types of mutants which produced mainly 10-carboxy-13-deoxocarminomycin, 10-methoxycarbonyl-13-deoxocarminomycin, their 11-deoxy derivatives or a precursor aglycone, respectively. In this paper, all the anthracycline components produced by the parent strain and its two known blocked mutants, a daunorubicin producer and a 11-deoxydaunorubicin producer, are also determined by HPLC and five new components are isolated. Cytotoxicities in vitro of all the components against L1210 cell culture are also described.

Animals↗
PubMed1992

Production of new anthracycline antibiotics 1-hydroxy-oxaunomycin and 6-deoxyoxaunomycin by limited biosynthetic conversion using a daunorubicin-negative mutant.

A limited biosynthetic conversion of some known anthracyclinones using a specific daunorubicin-nonproducing mutant provided four new anthracycline antibiotics: 1-Hydroxy-10-methoxycarbonyl-13-deoxocarminomycin; 1-hydroxy-13-deoxocarminomycin; 1-hydroxyoxaunomycin and 6-deoxyoxaunomycin. Their isolation and purification from bioconversion broth, structural determination and antitumor activities against leukemic L1210 cells are described.

Animals↗
PubMed1992

Photochemically obtained N-demethyl derivatives of anthracyclines.

New N-monodemethyl and N-didemethyl derivatives were obtained from seven N-dimethylamino sugar (rhodosamine)-containing anthracyclines by photochemical reaction and their in vitro bioactivities against L1210 cell culture were compared with those of their N-dimethyl parent compounds. N-Demethyl derivatives obtained from betaclamycin T (7-O-rhodosaminyl-beta-rhodomycinone) were much more cytotoxic while those from the other six antibiotics were rather less active as compared with their parent compounds. The N-demethylation also gave a considerably greater decrease in the inhibitory activity on RNA synthesis as compared to DNA synthesis, so that the N-demethyl derivatives showed smaller IC50 ratios on DNA/RNA than their parent compounds.

Animals↗
PubMed1992

Production of new anthracycline antibiotics by microbial 4-O-methylation using a specific daunorubicin-negative mutant.

Microbial 4-O-methylation using a specific daunorubicin-blocked, nonproducing mutant provided the new anthracycline antibiotics 4-O-methylbetaclamycin T, 4-O-methylyellamycin A and 4-O-methyl-13-hydroxyoxaunomycin, from which 4-O-methyloxaunomycin and 4-O-methyl-6-deoxyoxaunomycin were then prepared by further photochemical N-demethylation. Antitumor activities in vitro and in vivo against L1210 cells were compared with those of their 4-O-demethyl derivatives. It was found that all the 4-O-methyl derivatives had a markedly reduced cytotoxicity in vitro as compared with the 4-O-demethyl compounds. However, some of them were endowed with a significantly improved antitumor activity in vivo.

Animals↗
PubMed1992

[Aminoglycosides resistance of methicillin-resistant Staphylococcus aureus].

In the last decade, there has been a dramatic increase in the isolation frequency of methicillin-resistant Staphylococcus aureus (MRSA) in Japan. Especially, a high incidence of multiple resistant MRSA strains has been reported. These strains are resistant not only to beta-lactams but to aminoglycosides and macrolides. About 90% of MRSA strains were resistant to gentamicin (GM) and/or tobramycin (TOB), producing an aminoglycoside modifying enzyme, mainly, APH (2")/AAC (6) and/or AAD (4',4"). Based on these modifying enzymes produced, MRSA strains were classified into three groups; group 1 produced APH (2")/AAC (6), belonging to phage group I and coagulase IV, group 2 produced AAD (4',4"), belonging to phage group III and coagulase II, and group 3 produced APH (2")/AAC (6) and AAD (4',4"), belonging to phage group III and coagulase II. The epidemiological results suggest that MRSA strains changed from group 1 to group 2, and then to group 3. Recently, arbekacin (ABK), a new anti-MRSA aminoglycoside, has been introduced into clinical practice. ABK shows a potent activity to GM-resistant strains, due to poorly modification by APH (2")/AAC (6'). However, there were few ABK- and GM-resistant strains in clinical isolates. These strains produced a higher amount of the enzyme than ABK-susceptible and GM-resistant strains. This observation suggests that ABK-resistant strains might be derived from GM-resistant strains by mutation of the gene coding APH (2")/AAC (6').

Acetyltransferases↗
PubMed1992

[Effect of shakuyaku-kanzo-to on serum estrogen levels and adrenal gland cells in ovariectomized rats].

The aim of this study is to investigate the effect of the traditional herbal medicine, Shakuyaku-Kanzo-To (SKT) on oophorectomized (OVX) rats. In an in vivo experiment, OVX rats were orally given SKT (low dose group: 45 mg/kg b.w./day, high dose group: 450 mg/kg b.w./day) every day for 2 weeks. Serum dehydroepiandrosterone-sulfate (DHEA-S) and estrone (E1) levels of the low and high dose groups were higher than those of the control given vehicle. Serum 17 beta-estradiol (E2) levels only in the low dose group were higher than those of the control. In an in vitro experiment, adrenal gland cells of OVX rats were incubated with media containing SKT or Shakuyaku(S) or Kanzo(K) for 72-h. DHEA-S production was increased in the SKT 1,000 micrograms/ml and K 500 micrograms/ml group in comparison with the control. At the conclusion of this period, the cells were reincubated for an additional 8-h interval in an androstenedione (delta 4-A, 10(-7) M)-supplemented medium. Aromatase activity assessed by the conversion of delta 4-A to E1 or E2 was not increased in the SKT 1,000 micrograms/ml group. These results indicate that SKT increases DHEA-S, a precursor of estrogen, and brings about an increase in serum estrogen concentrations in OVX rats.

Administration, Oral↗
PubMed1992

[Myelodysplastic syndrome associated with marked eosinophilia and basophilia].

Myelodysplastic syndrome (refractory anemia with excess of blasts; RAEB) with marked basophilia and eosinophilia is described. An 82-year-old male was admitted to our hospital because of severe normocytic normochromic anemia (Hb 5.6 g/dl). The white cell count was 9,200/microliters with marked basophilia (34.5%) and eosinophilia (19.5%). The bone marrow aspiration also revealed both basophilia and eosinophilia, with blast contents of 9%. Diagnosis of RAEB was established. Although the treatment with red cell transfusion and ubenimex (Bastatin) was started, anemia was not improved. A karyotype of the bone marrow cells from this patient showed 47, XY, +8, i (17q), which has been observed as additional chromosomal abnormalities in blastic crisis of chronic myelogenous leukemia. The diagnosis of CML was not compatible with this case, because Ph1 chromosome and bcr gene rearrangement were negative. It is concluded that eosinophilia and basophilia might be derived from clonal abnormalities associated with MDS.

Aged↗
PubMed1991

Inhibition of the first ovulation and ovarian prostaglandin F2 alpha metabolism by danazol in rats.

The present study was conducted to investigate the mode of action of danazol by monitoring the first ovulation, serum luteinizing hormone (LH) levels and ovarian prostaglandin (PG) F2 alpha metabolism in pregnant mare serum gonadotropin (PMSG)-primed immature female rats. When danazol (750 mg/kg) was given p.o. once a day for 5 days (day 24-28), the occurrence of the first ovulation, the increase in capacity to form 13,14-dihydro-PGF2 alpha and PGF2 alpha levels induced by PMSG (5 IU) injected on day 26 were clearly inhibited on day 29. Danazol also markedly suppressed the LH surge occurring on day 28. Although the danazol-induced blockage of ovulation was restored by injection of human chorionic gonadotropin, the number of oocytes was significantly decreased as compared with that of controls. The present data indicate that the inhibitory actions of danazol on ovulation and ovarian PGF2 alpha metabolism may occur via some direct effects on the ovary in addition to the suppression of gonadotropin release from the pituitary gland.

Animals↗
PubMed1991

Basic fibroblast growth factor in rat corpus luteum stimulates prostaglandin F2-alpha production.

Rat luteal cells (LC) were incubated with or without basic fibroblast growth factor (bFGF) in a serum-free medium. Prostaglandin F2 alpha (PGF2 alpha) production was stimulated in a dose-dependent manner at 0.03-1 ng/ml of bFGF. One ng/ml of bFGF caused approximately 5-fold the increment of PGF2 alpha at every stage of LC after 48 hrs of incubation. bFGF also raised progesterone secretion from LC, and this stimulatory effect on progesterone was more distinguishable in an early-, than a middle- and a late-stage. Additionally, bFGF concentration throughout the luteal phase was assessed using western blot analysis. The protein with typical molecular weight 18 kDa form was in high concentration throughout the luteal phase. These results suggest that bFGF may play a role in the regulation of PGF2 alpha and progesterone production as autocrine, but not in mitosis in corpus luteum.

Animals↗
PubMed1991

Energy metabolism of the liver in brain dead dogs assessed by 31P-NMR spectroscopy and arterial ketone body ratio.

The changes in hepatic energy state were assessed by 31P-nuclear magnetic resonance spectroscopy (31P-MRS) and arterial ketone body ratio (AKBR) in brain dead dogs. 31P-MRS and AKBR were measured before and at 3 hours after brain death. Wiggers' shock model was employed to compare the energy metabolism during hypotension. 1) The brain death model: Systemic blood pressure changed from 178.3/115.0 mmHg (mean) in the control period, to 259.5/162.5 mmHg during Cushing phenomenon (CU period) and to 63.3/51.7 mmHg after completion of brain death (BD period). beta-ATP/Pi increased from 1.27 +/- 0.14 (mean +/- SEM) to 1.46 +/- 0.16 in the early CU period, and then decreased to 1.11 +/- 0.15 at 60 minutes after BD, followed by a gradual increase to 1.33 +/- 0.13 at 3 hours after BD. Intracellular pH (pHi) increased alkaline to the control value. AKBR decreased from 1.10 +/- 0.26 to 0.46 +/- 0.15 in the CU period (p less than 0.05) and then increased to 1.48 +/- 0.25 after BD. 2) Wiggers' shock model: Systemic blood pressure was 190.0/112.5 mmHg in the control period, 83.8/51.3 mmHg during exsanguination (EX period) and 185.0/117.0 mmHg after retransfusion (RT period). beta-ATP/Pi decreased from 1.17 +/- 0.13 to 0.61 +/- 0.10 in the EX period (p less than 0.05) and increased to 1.37 +/- 0.08 in the RT period. The pHi deviated from 7.33 +/- 0.07 to 6.82 +/- 0.14 in the EX period (p less than 0.01) and to 7.51 +/- 0.21 in the RT period. AKBR decreased from 1.00 +/- 0.11 to 0.21 +/- 0.04 in the EX period and increased to 1.08 +/- 0.12 in the RT period. The energy metabolism of the liver was well maintained in the state of brain death in spite of remarkable hypotension, although that was not the case with Wiggers' shock model. It was suggested that the combination of 31P-MRS and AKBR was useful for the evaluation of graft liver viability.

Adenosine Triphosphate↗
PubMed1991

Hepatic energy status in hypotension of different aetiologies in dogs.

1. The alterations in hepatic energy metabolism in hypotension induced by the administration of trimetaphan camsylate (Arfonad) were investigated in comparison with those produced by hypotension resulting from massive haemorrhage by measuring the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, and other indices of hepatic energy metabolism together with simultaneous measurement of hepatic blood flow in dogs. 2. Mean arterial blood pressure was decreased from 130 mmHg to 60 mmHg by the continuous intravenous infusion of trimetaphan camsylate or by the use of Wiggers' shock model. In hypotension induced by trimetaphan camsylate, the arterial ketone body ratio, ATP and total adenine nucleotide concentrations and energy charge were maintained at near-control values throughout the experimental period. By contrast, the arterial ketone body ratio decreased from 1.04 +/- 0.09 to 0.29 +/- 0.06 at 3 h after haemorrhage in Wiggers' shock model (P less than 0.01). The ATP and total adenine nucleotide concentrations and energy charge also decreased significantly in this model (P less than 0.05). The difference in hepatic energy status was also shown by data from 31P nuclear magnetic resonance spectroscopy. 3. During hypotension, portal venous and total hepatic blood flows diminished significantly compared with the control values in each group (P less than 0.01). Although there was no significant difference in total hepatic flow between the two groups, the portal venous blood flow in hypotension induced by trimetaphan camsylate was significantly higher than that in Wiggers' shock model (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Increased activities of thymidylate synthetase and thymidine kinase in human thyroid tumors.

Thymidylate synthetase (TS) is known to catalyse the methylation of deoxyuridine monophosphate (dUMP) for the de novo synthesis of deoxythymidine monophosphate (dTMP). Thymidine kinase (TK) catalyzes the formation of dTMP by the phosphorylation of thymidine via the pyrimidine salvage pathway. High TS and TK activities have been observed in rapidly proliferating tissues. Both TS and TK activities in human thyroid adenocarcinoma increased to approximately 2-fold that in normal thyroid tissue. The thyroid TK isozymes can be separated into two types by DEAE-cellulose column chromatography. One of them is associated with the cytosol cell fraction of rapidly proliferating cells, such as fetal or neoplastic cells. Its activity is not affected by low concentration of deoxycytidine triphosphate (dCTP), and its molecular weight and Km value for thymidine are 120 kD and 0.5 x 10(-6) M, respectively. The average activity of this cytosol-associated isozyme in thyroid adenocarcinoma was increased slightly to 2.3-fold that of normal thyroid tissue. These results obtained from the activities of TK and its isozyme may be indicative of the slow-growing property of thyroid adenocarcinoma compared to mammary or colonic adenocarcinoma, which has high activities of TK and its isozyme.

Adenocarcinoma↗
PubMed1991

The clinical significance of the arterial ketone body ratio as an early indicator of graft viability in human liver transplantation.

Arterial ketone body ratio (AKBR) was measured sequentially in 84 liver transplantations (OLTx). These transplantation procedures were classified into 3 groups with respect to graft survival and patient condition at the end of the first month (Group A, the grafts survived longer than 1 month with satisfactory patient condition; Group B, the grafts survived longer than 1 month but the patients were ICU-bound; Group C, the grafts were lost and the patients died or underwent re-OLTx). In Group A, the AKBR was elevated to above 1.0 by the second postoperative day. In Group B, the AKBR was elevated to above 0.7 but stayed below 1.0 during this period. In Group C, the AKBR remained below 0.7 longer than 2 days after operation. Although conventional liver function tests showed significant increases in Groups B and C as compared with Group A, they were less specific in predicting ultimate graft survival.

Adolescent↗