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Biomedical subjects

M Sakata

Publications and source records attributed to M Sakata.

At least 145 records · Page 8Linked to original sources
PubMed1994

Clinicopathological characteristics of p53 overexpression in endometrial cancers.

Using immunohistochemical methods, we analyzed the association between nuclear p53 overexpression and various clinicopathological parameters in patients with endometrial cancers. Formalin-fixed and paraffin-embedded tissue sections from 139 cases of endometrial cancer (endometrioid type, 126; serous papillary type, 12; and clear-cell type, 1) were stained with anti-p53 monoclonal antibody (MAb) DO7. Overexpression of p53 was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, serous papillary type and a personal history of cancer. Lymph-node metastasis was also related to p53 overexpression with marginal significance. Survival curves determined by the Kaplan-Meier method and univariate analysis showed p53 overexpression to be associated with a poor outcome in endometrial cancer patients. However, multivariate analysis using the stepwise Cox proportional-hazard model showed that whereas lymph-node metastasis, a personal history of cancer and muscular invasion were related to poor survival rates, p53 overexpression was not. Consequently, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial cancer, although a still larger sample of patient material would be required to assess this issue definitively.

Adult↗
PubMed1994

Pharmacokinetic and biotransformation studies of ormaplatin in conjunction with a phase I clinical trial.

Ormaplatin is a second-generation platinum (Pt) analogue with in vitro activity against some cisplatin-resistant malignant cell lines. We have evaluated the pharmacokinetics and biotransformations of ormaplatin during a phase I trial in which ormaplatin was administered by daily 30-min infusions on 5 consecutive days every 28 days. Sixteen patients received 25 courses at doses ranging from 5.0 to 11.6 mg/m2 per day. Pharmacokinetic parameters determined for ultrafilterable Pt measured by atomic absorption spectrophotometry revealed a short half-life (t1/2 16 min), moderate volume of distribution (Vd 12 l/m2), and relatively fast systemic clearance (Cls 544 ml/min per m2). Cls and percentage of drug unbound decreased during the 5-day administration period. Average systemic exposure increased with dose; however, inter-individual variability in Cls produced overlap in systemic exposure between the dose levels. The major active biotransformation product [PtCl2(dach)] was evaluated at the highest dose level by HPLC. This product decayed monoexponentially with a mean t1/2 of 13 min and a higher degree of pharmacokinetic variability than that of ultrafilterable Pt at this dose. No unreacted ormaplatin was detected; however, several inactive biotransformation products persisted for at least 120 min. Approximately 32% of the dose was excreted in the urine during the first day, one-third of this during the initial 1.5 h. The human pharmacokinetic characteristics of ormaplatin resemble those of cisplatin; however, additional study will be required to discern which analyte of ormaplatin correlates best with clinical effects.

Adult↗
PubMed1994

The hypothalamic-pituitary-ovarian axis in patients with endometriosis is suppressed by leuprolide acetate but not by danazol.

OBJECTIVE: To investigate the effects of leuprolide acetate (LA), a GnRH agonist (GnRH-a), and of danazol on the hypothalamic-pituitary-ovarian axis in patients with endometriosis. DESIGN: Ten patients were divided into LA and danazol treatment groups. MEASURES: Serum levels of E2, immunoreactive and bioactive LH, pulsatility of LH, and gonadotropins release by GnRH. Changes in serum E2 levels by hMG administration during LA treatment. RESULTS: Serum E2 level decreased to near castrated levels during the LA treatment, while it remained unchanged during the danazol treatment. Leuprolide acetate administration resulted in a significant suppression of the serum level of bioactive LH, of the pulsatility of LH release, of the pituitary response to GnRH injection, and of the elevation in the serum E2 level by hMG administration, but danazol treatment did not show these suppressive effects. CONCLUSION: Our results suggest that the hormonal actions of LA and danazol on endometriosis are different from each other, especially in the suppression of serum E2 level.

Adult↗
PubMed1994

Mouse placental cells secrete immunoreactive growth hormone-releasing factor.

The initial objective of this study was to establish a placental cell culture system in which the secretion of mouse growth hormone-releasing factor (mGHRF) could be examined during a several-day period. To determine when during pregnancy placental cells begin to express mGHRF, Northern blot analysis was carried out on total RNA from placentas collected on Days 6, 9, 11, 13, 15, 17, and 18 of pregnancy. Mouse GHRF mRNA could be detected as early as Day 11 of pregnancy. Its steady-state levels increased to maximum values on Days 15-17 and then declined slightly on Day 18. Placentas from Day 12 of pregnancy were selected for cell culture. The basal zone and labyrinth were dispersed in collagenase, and the cells were fractionated on a Percoll gradient. Two bands of cells were selected for further study. Both released significant amounts of immunoreactive mGHRF during a 5-day culture period. Effects of prolonged exposure of the cells to 8-bromo-cAMP and to agents that elevate intracellular cAMP concentration were then examined. Treatment of the cells with 0.5 mM 8-bromo-cAMP resulted in a significant decrease in the mGHRF concentration of the medium by the second day of culture. Mouse GHRF secretion was also inhibited by treatment of the cells with 100 ng/ml cholera toxin or 0.1 mM forskolin. The effect of 8-bromo-cAMP was concentration-dependent, with 0.1 mM being the lowest concentration that was active. 8-Bromo-cAMP treatment also reduced the steady-state level of mGHRF mRNA in the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm in a swine model.

BACKGROUND: The intracellular mechanism of coronary artery spasm is still unknown. The pathway mediated by protein kinase C (PKC) is an important intracellular process of various cellular responses, including vascular smooth muscle contraction. Thus, we examined the role of the PKC-mediated pathway in the pathogenesis of coronary artery spasm in our in vivo swine model. METHODS AND RESULTS: Seven Göttingen miniature pigs underwent coronary balloon injury and x-ray irradiation to induce atherosclerotic lesion. After 6 to 18 months, intracoronary serotonin (3 micrograms/kg) or histamine (3 micrograms/kg) repeatedly induced coronary artery spasm at the atherosclerotic site. At the spastic site, intracoronary administration of phorbol-12,13-dibutyrate (PDBu) (10(-9) mol/kg), a PKC-activating phorbol ester, also induced coronary artery spasm, which was completely blocked by pretreatment with intracoronary staurosporine (10 micrograms/kg), a PKC inhibitor. Intracoronary administration of an inactive phorbol ester, phorbol-12,13-didecanoate (10(-9) mol/kg), did not induce coronary vasoconstriction. Coronary artery spasm induced by the autacoids was significantly augmented by pretreatment with intracoronary PDBu and partially inhibited by staurosporine. Intracoronary administration of Bay K 8644 (10 micrograms/kg), a dihydropyridine-sensitive L-type calcium channel agonist, also induced coronary artery spasm at the spastic site, which was significantly inhibited by pretreatment with intracoronary staurosporine or nifedipine (0.1 mg/kg). CONCLUSIONS: These results suggest (1) the PKC-mediated pathway is importantly involved in the pathogenesis of coronary artery spasm, (2) activation of the PKC-mediated pathway partially accounts for serotonin- and histamine-induced coronary artery spasm, and (3) at the spastic site, calcium influx through dihydropyridine-sensitive L-type calcium channel and/or calcium sensitivity of the contractile proteins may be augmented by the PKC-mediated pathway.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Involvement of autocrine mechanism of transforming growth factor-beta in the functional differentiation of pregnant mouse mammary gland.

We studied the presence and possible role of the autocrine mechanism of transforming growth factor-beta (TGF-beta) in pregnant mouse mammary gland. Northern blot analysis revealed the expression of the TGF-beta 1 gene transcript at 2.5 kb in mammary epithelial cells isolated from virgin and mid-pregnant mice. The TGF-beta activity was higher in the conditioned medium from mid-pregnant mouse mammary explants than that from virgin explants by a bioassay system using mink lung epithelial cells. A binding study using [125I]TGF-beta 1 as a ligand showed that pregnant mouse mammary epithelial cells possessed a single class of high-affinity TGF-beta 1 binding sites (Kd = 28.0 pmol/l, 1.2 x 10(4) sites per cell). These results suggested the presence of a TGF-beta autocrine mechanism in pregnant mouse mammary epithelial cells. Next, we examined the effect of TGF-beta 1 on the functional differentiation of pregnant mouse mammary gland. Transforming growth factor-beta 1 inhibited alpha-lactalbumin production in cultured mammary explants from mid-pregnant mice in a dose-dependent manner without inhibiting DNA synthesis. All these results suggest that TGF-beta may play a role in regulating the functional differentiation of mouse mammary glands during pregnancy.

Animals↗
PubMed1994

Increase in the capability of interleukin 2 gene-transduced renal cell carcinoma cells to induce cytotoxic lymphocytes.

The immunogenicity of human cancer cells transfected with interleukin 2 (IL-2) gene, a potent vaccine candidate, has not yet been fully investigated. Human renal cell carcinoma (RCC) cells transduced with human IL-2 gene (RCC-IL-2) were investigated in vitro for the capability to induce lymphokine-activated killer (LAK) or cytotoxic T lymphocyte (CTL) activity in peripheral blood mononuclear cells (PBMC) or tumor-infiltrating lymphocyte (TIL). The RCC-IL-2 cells stimulated PBMC to demonstrate LAK activity, and also stimulated autologous TILs to proliferate and exhibit cytotoxicity relatively restricted to autologous tumor cells. In contrast, both parental RCC and RCC transduced with neomycin gene alone failed to induce these activities. These results indicate that RCC-IL-2 cells are more potent than the other RCC cells with regard to inducing cytotoxic lymphocytes against autologous tumor cells.

Base Sequence↗
PubMed1994

Phenthoate metabolites in human poisoning.

Five metabolites were detected in the plasma and urine of a patient following ingestion of the organophosphate insecticide, phenthoate. Intact phenthoate was detected only in gastric lavage fluid. After methylation of acidic extracts of plasma and urine, phenthoate acid, demethyl phenthoate, demethyl phenthoate oxon acid, demethyl phenthoate S-isomer, and demethyl phenthoate acid S-isomer were identified with synthesized phenthoate analogues by gas chromatography and gas chromatograph-mass spectrometry. The main metabolites were phenthoate acid and demethyl phenthoate oxon acid. Although demethyl phenthoate oxon acid was a significant metabolite, no phenthoate oxon, phenthoate oxon acid or demethyl phenthoate oxon were detected. If the oxon was formed in the patient, it may have been rapidly degraded by carboxylesterase or glutathione transferase to demethyl phenthoate oxon acid.

Chromatography, Gas↗
PubMed1994

[A successful surgical correction of the intermediate type of common atrioventricular orifice--report of an adult case].

A 42-year-old female was admitted to our hospital because of exertional dyspnea. Preoperative color Doppler echocardiogram revealed massive left to right shunt through the ostium primum defect, moderate mitral and tricuspid regurgitation, and trivial shunt via the small ventricular septal defect. Preoperative cardioangiogram also demonstrated goose neck deformity of the left ventricle. At the operation, the piece of atrioventricular valve fused on the summit of the small scooped ventricular defect was detected, and the total correction consisted of patch closure of the ostium primum defect and mitral and tricuspid valvuloplasty was performed. Postoperative course was uneventful. This is the first adult case reported in Japan who was operated on for the intermediate type of common atrioventricular orifice.

Adult↗
PubMed1993

Autocrine growth mechanism by transforming growth factor (TGF)-beta 1 and TGF-beta 1-receptor regulation by epidermal growth factor in a human endometrial cancer cell line IK-90.

Transforming growth factor-beta 1 (TGF-beta 1) enhanced cell proliferation in a concentration-dependent manner in a human endometrial cancer cell line, IK-90. Scatchard analysis of TGF-beta 1 receptor in IK-90 cells, using 125I-TGF-beta 1 as a ligand, revealed the presence of a class of high-affinity TGF-beta 1 receptors (2,000 sites per cell, KD = 74pM). Moreover, IK-90 cells produced and secreted TGF-beta 1: TGF-beta 1 messenger RNA was detected at 2.5 and 4.0 kb by Northern-blot analysis using 32P-labeled TGF-beta 1 cDNA as a probe, and TGF-beta 1 activity in conditioned medium by the inhibition of 3H-thymidine uptake into CCl 64 mink lung epithelial cells. We investigated the regulation of TGF-beta 1 receptor by 4 kinds of growth factor: epidermal growth factor (EGF) but not TGF-beta 1, insulin or insulin-like growth factor-1 increased the level of TGF-beta 1 binding sites in a concentration- and time-dependent manner. These findings suggest that TGF-beta 1 may be a potential autocrine growth factor in a human endometrial cancer cell line IK-90 and that this autocrine mechanism may be affected by EGF.

Adult↗
PubMed1993

Ovariectomy increases the level of estrogen receptor mRNA and estrogen receptor binding sites in female rat adipose tissue.

The roles of estrogen in the changes in estrogen receptor (ER) mRNA and ER binding sites in rat adipose tissue were studied in female rats. To elucidate the mechanism(s) behind ovariectomy (OVX)-induced obesity, the levels of ER mRNA and ER binding sites in adipose tissue were analyzed three weeks after OVX using Northern blot analysis of ER mRNA and the [3H]E2 binding assay, respectively. OVX induced an increase in body weight, and replacement of estradiol (E2) prevented that increase. Significant increases in the amounts of ER mRNA and in [3H]E2-specific binding were observed after OVX, and E2 replacement reduced both of those increases. These results suggest that E2 may regulate rat obesity directly through ER in adipose tissues.

Adipose Tissue↗
PubMed1993

Metabolic interaction of ethanol and cyclohexanone in rabbits.

The interaction of ethanol (EtOH) and cyclohexanone (CHN) metabolism was studied to demonstrate the influence of alcohol beverage in cyclohexanone poisoning. Rabbits were administered CHN and EtOH separately or together, and the plasma concentration of CHN and cyclohexanol (CHL), a metabolite of CHN, and blood concentrations of EtOH were measured at various times. When CHN alone was administered orally, the time to maximum plasma concentration (Tmax) of CHN was as short as 15 min, but that of CHL was 120 min. The short Tmax of CHN was considered to be due to the first-pass effect. The plasma concentration of CHL was much greater than that of CHN. On the other hand, when the same amount of molar CHL was administered in rabbits for sake of comparison, only small amounts of CHN were detected in plasma. The interconversion between CHN and CHL at the time of equilibration tended to shift predominantly toward the formation of CHL, whose plasma concentration ratio was about 1:6 to 1:8. The coadministration of EtOH decreased the plasma concentration of CHN and increased that of CHL more than the administration of CHN alone. The blood concentration of EtOH was also decreased with the coadministration of CHN. The coadministration of EtOH with CHN demonstrated an acceleration in the metabolism of both CHN and EtOH, which may be due to an increase in the concentrations of the alcohol dehydrogenase-NADH and -NAD complexes.

Administration, Oral↗
PubMed1993

Glibenclamide, a putative ATP-sensitive K+ channel blocker, inhibits coronary autoregulation in anesthetized dogs.

We tested the hypothesis that ATP-sensitive K+ channels are involved in the mechanism mediating coronary autoregulation in open-chest dogs. We perfused the left anterior descending coronary artery with arterial blood from an extracorporeal circuit and measured steady-state coronary blood flow (CBF) with stepwise changes in coronary perfusion pressure (CPP) between 50 and 150 mm Hg during an intracoronary infusion of vehicle or glibenclamide (a putative blocker of ATP-sensitive K+ channels). CBF was relatively stable over CPP between 50 and 110 mm Hg during vehicle infusion, indicating the presence of autoregulation at the CPP range. During glibenclamide infusion (10 micrograms.min-1 x kg-1), CBF progressively decreased with reduction in CPP below 110 mm Hg, whereas the CPP-CBF relation at CPP above 110 mm Hg was not altered by glibenclamide. The autoregulation index [1-(delta F/F)/(delta P/P), where F indicates CBF and P indicates CPP] was greater than 0 over the CPP range between 50 and 100 mm Hg during vehicle infusion and was less than 0 during glibenclamide infusion. Glibenclamide did not alter systemic arterial pressure, heart rate, left ventricular pressure, and changes in regional myocardial oxygen consumption associated with changes in CPP. In the absence of glibenclamide, the CPP-CBF relation was reproducible in the repeated studies for time control. These results suggest that ATP-sensitive K+ channels play an important role in mediating coronary autoregulation at the lower range of CPP in the blood-perfused dog heart.

Adenosine Triphosphate↗
PubMed1993

Reduction of endotoxin contamination of various crude vaccine materials by gram-negative bacteria using aminated poly(gamma-methyl L-glutamate) spherical particles.

We describe a method for the removal of endotoxins from various crude antigen solutions originating from gram-negative bacteria using aminated poly(gamma-methyl L-glutamate) (PMLG) spherical particles. The aminated PMLG adsorbents showed high affinity for various purified endotoxins at an ionic strength of mu = 0.1. The endotoxin-adsorbing capacity of the adsorbent increased with increase in the amino-group content of the adsorbent. The adsorbent (3.2 meq/g amino-group content) showed the highest affinity for endotoxin at ionic strengths ranging from mu = 0.025-0.8. The adsorption of Bordetella pertussis antigen to the adsorbent decreased with increasing amino-group content of the adsorbent at an ionic strength of mu = 0.2. The adsorption of B. bronchiseptica protein to the adsorbent increased with increasing amino-group content of the adsorbent, but decreased with increasing ionic strength. The adsorbent (3.2 meq/g of amino-group content) selectively reduced endotoxin in crude antigen solutions originating from gram-negative bacteria, B. pertussis, B. bronchiseptica and Pasteurella multocida, even at a high ionic strength (mu = 0.2-0.4) without affecting the recovery of the protective antigens.

Adsorption↗
PubMed1993

[Studies on the constituents of edible and medicinal plants. IV. Determination of 4-O-methylpyridoxine in serum of the patient with gin-nan food poisoning].

The serum 4-O-methylpyridoxine (MPN) levels in a 21 months-old patient with gin-nan food poisoning were determined by HPLC. The blood of the patient was taken at 8.5 and 15.5 h after taking about 50 ginkgo albumens. After deproteinization of the serum, the supernatant was pretreated with Sep-pak C18 cartridge and was applied to HPLC. HPLC was performed with a Hibar LiChrosorb RP-18 (4.0 mm i.d. x 250 mm, 7 microns) using a fluorescence detector (wave length of excitation and fluorescence; 290 and 400 nm, respectively). The serum MPN level was determined by the absolute calibration method. The determination limit of MPN in the serum was 0.05 micrograms/ml. The serum MPN concentration was 0.09 micrograms/ml at 8.5 h after taking ginkgo seeds, and was less than the determination limit of MPN (0.05 micrograms/ml) at 15.5 h. MPN, isolated from the seed of Ginkgo biloba L., is responsible for "gin-nan food poisoning," and its cardinal symptoms are mainly tonic and/or clonic convulsions and loss of consciousness. Infants are particularly vulnerable. This method may be available for proving the gin-nan food poisoning, chemically.

Chromatography, High Pressure Liquid↗