Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 523 records · Page 29Linked to original sources

PubMed1998

Study of the effects of dispase in the chemotherapy of multicellular tumour spheroids of small-cell lung carcinoma in man.

Multicellular tumour spheroids (MTS), diameter 650 microm, from PC-6, SBC-1 and NCL-H60 small-cell lung carcinoma cell-lines in man were prepared by the liquid overlay culture method and used to study the influence of treatment with dispase (bacterial neutral protease from Bacillus polymyxa, 1000 units mL(-1)) on the effectiveness of carboplatin, as determined by colony-forming assay. When carboplatin alone was used on monolayers the curve of survival fraction against concentration was exponential in shape, indicating that the drug was active against the monolayer. When MTS were treated with medium concentrations (10(-5) and 10(-4) M) of carboplatin alone the survival fraction-concentration curve showed that the effectiveness of the treatment was less than that against the monolayer. On treatment of MTS with carboplatin and dispase the survival fraction-concentration curve was similar to that obtained for the monolayer and the survival fraction of the core of the MTS was also less than when carboplatin alone was used. These results imply that dispase dissolves the intercellular matrix of the MTS enabling enhanced infiltration of carboplatin into the core of the MTS. Dispase thus indirectly increases the effectiveness of carboplatin.

Antineoplastic Agents↗

PubMed1998

In-vitro characterization of YM872, a selective, potent and highly water-soluble alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist.

The in-vitro pharmacological properties of (2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxal inyl)-acetic acid monohydrate, YM872, a novel and highly water-soluble alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor antagonist were investigated. YM872 is highly water soluble (83 mg mL(-1) in Britton-Robinson buffer) compared with 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX), 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM90K) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). YM872 potently inhibits [3H]AMPA binding with a Ki (apparent equilibrium dissociation constant) value of 0.096 +/- 0.0024 microM. However, YM872 had very low affinity for other ionotropic glutamate receptors, as measured by competition with [3H]kainate (high-affinity kainate binding site, concentration resulting in half the maximum inhibition (IC50) = 4.6 +/- 0.14 microM), [3H]glutamate (N-methyl-D-aspartate (NMDA) receptor glutamate binding site, IC50 > 100 microM) and [3H]glycine (NMDA receptor glycine-binding site, IC50 > 100 microM). YM872 competitively antagonized kainate-induced currents in Xenopus laevis oocytes which express rat AMPA receptors, with a pA2 value of 6.97 +/- 0.01. In rat hippocampal primary cultures, YM872 blocked a 20-microM AMPA-induced increase of intracellular Ca2+ concentration with an IC50 value of 0.82 +/- 0.031 microM, and blocked 300-microM kainate-induced neurotoxicity with an IC50 value of 1.02 microM. These results show that YM872 is a potent and highly water-soluble AMPA antagonist with great potential for treatment of neurodegenerative disorders such as stroke.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1998

Cloning, sequencing, and disruption of the Bacillus subtilis psd gene coding for phosphatidylserine decarboxylase.

The psd gene of Bacillus subtilis Marburg, encoding phosphatidylserine decarboxylase, has been cloned and sequenced. It encodes a polypeptide of 263 amino acid residues (deduced molecular weight of 29,689) and is located just downstream of pss, the structural gene for phosphatidylserine synthase that catalyzes the preceding reaction in phosphatidylethanolamine synthesis (M. Okada, H. Matsuzaki, I. Shibuya, and K. Matsumoto, J. Bacteriol. 176:7456-7461, 1994). Introduction of a plasmid containing the psd gene into temperature-sensitive Escherichia coli psd-2 mutant cells allowed growth at otherwise restrictive temperature. Phosphatidylserine was not detected in the psd-2 mutant cells harboring the plasmid; it accumulated in the mutant up to 29% of the total phospholipids without the plasmid. An enzyme activity that catalyzes decarboxylation of 14C-labeled phosphatidylserine to form phosphatidylethanolamine was detected in E. coli psd-2 cells harboring a Bacillus psd plasmid. E. coli cells harboring the psd plasmid, the expression of which was under the control of the T7phi10 promoter, produced proteins of 32 and 29 kDa upon induction. A pulse-labeling experiment suggested that the 32-kDa protein is the primary translation product and is processed into the 29-kDa protein. The psd gene, together with pss, was located by Southern hybridization to the 238- to 306-kb SfiI-NotI fragment of the chromosome. A B. subtilis strain harboring an interrupted psd allele, psd1::neo, was constructed. The null psd mutant contained no phosphatidylethanolamine and accumulated phosphatidylserine. It grew well without supplementation of divalent cations which are essential for the E. coli pssA null mutant lacking phosphatidylethanolamine. In both the B. subtilis null pss and psd mutants, glucosyldiacylglycerol content increased two- to fourfold. The results suggest that the lack of phosphatidylethanolamine in the B. subtilis membrane may be compensated for by the increases in the contents of glucosyldiacylglycerols by an unknown mechanism.

Amino Acid Sequence↗

PubMed1998

Chromatin remodeling mediated by Drosophila GAGA factor and ISWI activates fushi tarazu gene transcription in vitro.

GAGA factor is known to remodel the chromatin structure in concert with nucleosome-remodeling factor NURF in a Drosophila embryonic S150 extract. The promoter region of the Drosophila fushi tarazu (ftz) gene carries several binding sites for GAGA factor. Both the GAGA factor-binding sites and GAGA factor per se are necessary for the proper expression of ftz in vivo. We observed transcriptional activation of the ftz gene when a preassembled chromatin template was incubated with GAGA factor and the S150 extract. The chromatin structure within the ftz promoter was specifically disrupted by incubation of the preassembled chromatin with GAGA factor and the S150 extract. Both transcriptional activation and chromatin disruption were blocked by an antiserum raised against ISWI or by base substitutions in the GAGA factor-binding sites in the ftz promoter region. These results demonstrate that GAGA factor- and ISWI-mediated disruption of the chromatin structure within the promoter region of ftz activates transcription on the chromatin template.

Adenosine Triphosphatases↗

PubMed1998

Anti-inflammatory effects of mao-bushi-saishin-to in mice and rats.

Effects of Mao-Bushi-Saishin-to (MBS) on anti-inflammatory activities were examined in mice and rats. MBS significantly inhibited the increase in vascular permeability induced by acetic acid, the ear edema induced by arachidonic acid and phorbol ester, and the cutaneous extravasation induced by bradykinin and histamine. MBS, however, was not effective against the serotonin-induced cutaneous permeability increase in mice. MBS significantly inhibited carrageenin-induced hind foot edema and cotton pellet-induced granulation tissue growth in rats. These results show that MBS may exert anti-inflammatory effects through the underlying mechanism(s) of preventing mediator release from mast cells and macrophages.

Acetic Acid↗

PubMed1998

Complete caudate lobectomy: its definition, indications, and surgical approaches.

There are three ways to approach and resect the caudate lobe of the liver, that is; and isolated caudate lobectomy, a combined resection of the liver overlying the caudate lobe, and a transhepatic anterior approach by splitting parenchyma of the liver. We had two patients with neoplasms originating in the caudate lobe who underwent a complete caudate lobectomy. Both patients have been doing well without liver dysfunction. Although after the transhepatic anterior approach we anticipated an adverse effect from splitting the parenchyma of the liver, the postoperative course was uneventful and similar to that of the right side approach.

Adenocarcinoma↗

PubMed1998

Evidence of apoptosis induced by myocardial ischemia: A case of ventricular septal rupture following acute myocardial infarction.

Recent studies have reported that apoptosis may be induced by reperfusion injury following ischemia in cardiomyocytes. We present a case with evidence of apoptosis induced by myocardial ischemia without reperfusion. DNA fragmentation was demonstrated in the nuclei of the myocardial cells surrounding the ventricular septal rupture following acute myocardial infarction without reperfusion in the infarct-related left anterior descending coronary artery. This finding suggests that ischemia without reperfusion may induce apoptosis in myocardial cells.

Aged↗

PubMed1998

A morphological and morphometrical study of the retina in aging SAM mice.

We investigated whether neuronal cell loss occurred as a part of normal aging of the retina in the Senescence-Accelerated Mouse, strains SAMP1 and SAMR1, and in the BALB/c mouse. All three strains showed age-related atrophy of the retina after histologically normal development. Morphometrical study revealed the following facts. The rate of loss of photoreceptor cells in the peripheral retina was greater than in the central retina in all three strains. In the central retina, the rate of loss of photoreceptor cells was greater in the SAMP1 and SAMR1 mice than in the BALB/c mice. In the peripheral retinal, the SAMR1 and SAMP1 strains had fewer cells than the BALB/c strain at all ages, but the rate of loss of these cells did not differ among the three strains. The rate of loss of ganglion cells did not differ between the peripheral and central retinas in the three strains. The SAMR1 and SAMP1 strains had fewer ganglion cells in the peripheral retina than the BALB/c strain at all ages. Because the rate of age-related loss of these cells in SAMP1 mice was not accelerated, and they were short-lived, SAMP1 mice did not show marked age-related loss. On the contrary, the SAMR1 mice showed a marked loss of photoreceptor cells and ganglion cells late in life because of their longer life span, and we propose that this strain is a suitable animal model for the study of mechanisms of age-related loss of neuronal cells in the retina.

Aging↗

PubMed1998

Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells.

In vivo, vascular walls are exposed to mechanical stretch, which may promote atherogenesis. This study was designed to investigate the effect of mechanical stretch on the production and gene expression of cytokines in endothelial cells (ECs) of human umbilical veins. ECs were cultured on flexible silicone membranes and exposed to cyclic mechanical stretch. Although the secretion levels of interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, granulocyte (G) -colony stimulating factor (CSF), G and macrophage (M) -CSF, and M-CSF were not affected by cyclic stretch over 24 hours, the levels of IL-8 and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) were significantly increased by cyclic stretch. Northern blot analysis indicated that the mRNA levels of IL-8 and MCAF/MCP-1 were upregulated by cyclic stretch as a function of its intensity. Cytochalasin D, which disrupts the actin cytoskeleton, abolished the stretch-induced gene expression of IL-8 and MCAF/MCP-1. In contrast, neither inhibition of stretch-activated ion channels nor disruption of microtubules affected the induction of these chemokines by cyclic stretch. Northern blot analysis using enzyme inhibitors showed that phospholipase C, protein kinase C, and tyrosine kinase were involved in the stretch-induced gene expression of IL-8 and MCAF/MCP-1, whereas cAMP- or cGMP-dependent protein kinase was not. In conclusion, cyclic stretch enhanced the secretion and gene expression of IL-8 and MCAF/MCP-1 in a stretch-dependent fashion, and the integrity of the actin cytoskeleton and activities of phospholipase C, protein kinase C, and tyrosine kinase may be essential in the process of stretch-induced gene induction of IL-8 and MCAF/MCP-1.

Cells, Cultured↗

PubMed1998

New antidiabetic compounds, mangiferin and its glucoside.

Mangiferin (MF) and its glucosides (mangiferin-7-O-beta-glucoside) (MG) isolated from Anemarrhena asphodeloides Bunge rhizome, were tested for their antidiabetic activity in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus (NIDDM). MF and MG lowered the blood glucose level of KK-Ay mice after oral administration. However, no affect on the blood glucose level in normal mice was seen, indicating that MF and MG are useful in treating NIDDM. In addition, MF or MG improved hyperinsulinemia in KK-Ay mice. From these findings, it seems likely that MF and MG exert their its antidiabetic activity by increasing insulin sensitivity.

Animals↗

PubMed1998

Differential effects of cytotoxic drugs on mortal and immortalized B-lymphoblastoid cell lines from normal and Werner's syndrome patients.

We studied the effects of nine cytotoxic drugs on three groups of B-lymphoblastoid cell lines transformed by Epstein-Barr virus (EBV): group 1, mortal cell lines from normal individuals; group 2, immortalized cell lines from normal individuals with strong telomerase activity; group 3, mortal cell lines from Werner's syndrome (WS) patients. Aminoglycoside antibiotics and alkylating drugs showed significantly stronger cytotoxic effects on immortalized cell lines than on mortal cell lines or the cell lines before immortalization. In contrast, topoisomerase II inhibitors showed no difference or they tended to be less cytotoxic to immortalized cell lines. Mortal cell lines from normal individuals and WS patients showed no difference in sensitivity against all the drugs examined except for the topoisomerase I inhibitor, camptothecin, which had a stronger cytotoxic effect on WS cell lines than other cell lines. We discuss the mechanisms underlying these cytotoxic effects.

Aminoglycosides↗

PubMed1998

Circulating hepatocyte growth factor as an early marker of arterial thrombus formation.

This study was designed to measure circulating hepatocyte growth factor (HGF) in a rat model of arterial thrombosis. The carotid endothelial surface of rats was denuded with a balloon catheter and partially occluded. The amount of thrombus formation was expressed as the difference between the wet weights of paired treated and nontreated carotid arteries. Thrombus weight increased gradually up to 60 min after denudation. Plasma HGF did not increase before 30 min, but had significantly increased by 60 min compared with all previous measurements (p<0.05). Measurements of circulating HGF may be useful in the early diagnosis of arterial thrombosis.

Animals↗

PubMed1998

The AMPA-receptor antagonist YM90K reduces AMPA receptor-mediated excitotoxicity in rat hippocampal cultures.

The effects of YM90K on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitotoxicity were investigated using kainate, AMPA and cyclothiazide in rat hippocampal cultures. YM90K had neuroprotective actions against both kainate toxicity and cyclothiazide-enhanced AMPA toxicity. YM90K induced a parallel and rightward shift of both kainate and AMPA dose-response curves. The application of YM90K even 3 hr after the start of kainate exposure significantly reduced kainate toxicity. These results indicate that YM90K protects neurons against AMPA receptor-mediated toxicity at an agonist site on the AMPA receptor and that YM90K protects against AMPA receptor-mediated toxicity even if applied after neurotoxic insult.

Animals↗

PubMed1998

Germline cell formation in Drosophila embryogenesis.

The classical term germ cell determinant was defined to cover whole function of germ plasm, or morphologically remarkable cytoplasm localized in oocytes and germ cells. Since early 1970 consequential advances in technology, including microsurgery, genetic anatomy and gene manipulation, have allowed cytological and molecular analyses of pole plasm (germ plasm) in Drosophila embryos. A series of recent work has revealed that multiple factors or molecule species in pole plasm participate in a consecutive reactions resulting in germline formation. Two molecule species have been specified as playing roles in germline cell formation. One that participates in sequestering pole plasm from somatic environment is mitochondrial large ribosomal (mtlr) RNA, and the other involved in driving pole cells into the germline pathway is Nanos protein. Studies disclosed the roles of those two molecules are reviewed.

Animals↗

PubMed1998

Experimental dual infection of cesarean-derived, colostrum-deprived pigs with Mycoplasma hyopneumoniae and pseudorabies virus.

To determine whether pseudorabies virus (PRV) infection increases the severity of pneumonia by Mycoplasma hyopneumoniae, 18, 10-week-old Cesarean-derived, colostrum-deprived pigs were randomly assigned to 3 groups of 6 pigs each. Pigs in groups A and C were inoculated intranasally with M. hyopneumoniae at 10-week-old. At 11-week-old, pigs in groups B and C were inoculated intranasally with PRV. All pigs were initially seronegative for M. hyopneumoniae and PRV. Three pigs of each group were euthanized at 12-week-old, and remaining pigs at 14-week-old. At necropsy, gross lesions in the lung were observed in the pigs of groups A and C. On post-inoculation-week (PIW) 2 with M. hyopneumoniae (at 12-week-old), lung lesions were recognized in one of the 3 pigs in group A and all the pigs in group C. The mean percentage of the lung lesions were 0.1% in group A and 9.8% in group C. M. hyopneumoniae was isolated from broncho-alveolar lavage fluids (BALF) of pigs in group A with titer of 10(2) to 10(3) CCU/0.2 ml and in group C with titer of 10(5) to 10(6) CCU/0.2 ml. On PIW 4 (at 14-week-old), lung lesions were observed in all the pigs in groups A and C, and the mean percentage of the lung lesions were 8.3% in group A and 17.2% in group C. M. hyopneumoniae was isolated from BALF in group A with titer of 10(4) to 10(7) CCU/0.2 ml and in group C with titer of 10(6) to 10(7) CCU/0.2 ml. PRVs were isolated from nasal swab and tissue samples in groups B and C. After inoculation, antibody against M. hyopneumoniae was detected in groups A and C, and against PRV in groups B and C. Under the present experimental conditions, PRV infection appear to have effect on the severity of experimentally induced acute mycoplasmal pneumonia in young pigs.

Animals↗

PubMed1998

Vascular endothelial growth factor increased by pulmonary surgery accelerates the growth of micrometastases in metastatic lung cancer.

BACKGROUND: The use of surgery for metastatic lung cancer has been established recently and the indications have been extended to multiple and bilateral lung metastases. However, in some patients, secondary lung metastasis appears soon after the first pulmonary surgery, making curative treatment very difficult. Postoperative weakness of tumor angiogenesis suppression mechanisms seems to play an important role in the recurrence of lung metastases. To verify this hypothesis, we performed a clinical and an experimental study. RESULTS AND CONCLUSION: The clinical study revealed that serum vascular endothelial growth factor (VEGF), also known as vascular permeability factor, increased after pulmonary surgery. The experimental study showed that VEGF played an important role in the rapid growth of dormant micrometastases of the lung. These results suggested that the postoperative increase of VEGF disrupted angiogenesis suppression and induced the growth of dormant micrometastases early in the postoperative period. It was also demonstrated that this effect of VEGF on micrometastases was abolished by AGM-1470, an angiogenesis inhibitor. In conclusion, postoperative treatment with AGM-1470 might inhibit the early recurrence of malignant tumors.

Adult↗

PubMed1998

Surgical successful treatment of Cushing's syndrome in a pregnant patient complicated with severe cardiac involvement.

We encountered a case of a pregnant woman with adrenal causes of Cushing's syndrome who exhibited congestive heart failure as an initial symptom. Since the patient was also a diabetic, we treated her with high levels of diuretics and insulin. Echocardiography revealed a remarkable thickening of the left ventricle without asymmetric hypertrophy. The diagnosis of Cushing's syndrome caused by adrenal adenoma was confirmed by the endocrinological data and magnetic resonance imaging. The right adrenal adenoma was removed in the 28th week of pregnancy. After the operation, her congestive heart failure and hyperglycemia dramatically improved. Five weeks after the operation, she delivered a normal infant by caesarean section without complications. Only 4 months after delivery, the thickening of her left ventricle was normalized. We consider that the progression of her left ventricular hypertrophy induced by the changes in hemodynamic load during pregnancy may have been augmented by the excess of plasma cortisol. Operative therapy may be recommended for pregnant Cushing's syndrome patients with severe hypercortisolism complicating congestive heart failure.

Adenoma↗

PubMed1998

Pregnant woman with transient diabetes insipidus resistant to 1-desamino-8-D-arginine vasopressin.

We encountered a pregnant woman with transient diabetes insipidus which developed during the third trimester. A hypertonic saline infusion study did not concentrate the osmolality of urine. Her laboratory data showed hypokalemia, hyperreninemia, an increased concentration of plasma aldosterone and an increased urinary excretion rate of prostaglandin E2, which resembled hyperprostaglandin E-syndrome. T1-weighted magnetic resonance imaging of the posterior pituitary gland revealed decreased intensity. Polyuria reached 4-6 L daily, and urine osmolality remained dilute despite a lapse of four days since treatment with intranasal 1-desamino-8-D-arginine vasopressin (dDAVP: 10-25 microg every 12 h). The patient was conservatively managed without medical treatment, then delivered in the 38th week of pregnancy without complication. The osmolality of the patient's urine was higher than that of the plasma when tested 3 days postpartum. The abnormality of magnetic resonance imaging of the posterior pituitary gland disappeared at 6 months after delivery. We consider that subclinical nephrogenic diabetes insipidus in our patient was exacerbated during pregnancy.

Adult↗