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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 595 records · Page 33Linked to original sources
PubMed1995

Biological half-lives of zinc and manganese in rat brain.

The brains of rats injected intravenously with 65ZnCl2 or 54MnCl2 were subjected to high-resolution autoradiography. The distribution of 65Zn and 54Mn in each brain region gradually decreased from 6 days to 42 days for 65Zn and from 15 days to 60 days for 54Mn after the injection. The biological half-lives of Zn in each region studied were in the range of 16-43 days; the longest was observed in the amygdaloid nuclei. The regions where the long biological half-life was observed were consistent with the ones with the high density of Zn-containing neuron terminals reported previously. The biological half-lives of Mn in each region were 51-74 days; the longest were those in the hypothalamic nuclei and thalamus.

Animals↗
PubMed1995

Real-time PET analysis of metastatic tumor cell trafficking in vivo and its relation to adhesion properties.

Although a number of studies have indicated that highly metastatic cells tend to adhere more to target endothelium in vitro than low or non-metastatic cells, direct evidence about the correlation between cellular adhesiveness and organ disposition of the cells has not been obtained. Using positron emission tomography (PET), we have developed a novel technique that enables the non-invasive detection of the real-time tumor cell trafficking. The present study shows the correlation between trafficking of murine large cell lymphoma RAW117 and the adhesion properties of the cells in vitro. Cells accumulated in the liver time-dependently, and accumulation of RAW117-H10, liver metastatic subline cells, was more intense than that of RAW117-P, the parental cells, indicating that the metastatic potential is correlated with the in vivo accumulation of the cells in the target tissue. To examine whether the adhesion properties of the cell membrane determine the cell trafficking, we performed PET analysis after altering the adhesion properties on the cell membrane by means of cellular protein kinase C modulation, since the modulation of this enzyme is known to alter the surface adhesion molecules, i.e., those of the integrin superfamily. The treatment of RAW117-P with 12-O-tetradecanoylphorbol 13-acetate, which caused augmentation of adhesion to hepatic sinusoidal microvessel endothelial cells (HSE) in vitro, enhanced the hepatic accumulation of the cells in vivo. On the contrary, treatment of RAW117-H10 with the protein kinase C inhibitor H-7, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, which reduced the adhesion activity of the cells to HSE, suppressed their accumulation in the liver, although the suppression was observed only during the first 30 min after administration of the cells. These data suggest that the adhesion properties of metastatic lymphoma cells are critical for the accumulation of these cells in the target tissue.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Shc isoform-specific tyrosine phosphorylation by the insulin and epidermal growth factor receptors.

Insulin stimulation of Chinese hamster ovary cells expressing the human insulin and epidermal growth factor (EGF) receptors (CHO/IR/ER) resulted in the tyrosine phosphorylation of the 52-kDa Shc isoform with a relatively low extent of 46-kDa Shc tyrosine phosphorylation. In contrast, EGF stimulation resulted in the tyrosine phosphorylation of both the 52- and 46-kDa Shc isoforms. Consistent with these differences, Grb2 predominantly bound to the 52-kDa Shc isoform following insulin stimulation, whereas Grb2 associated with both the 52- and 46-kDa Shc isoforms after EGF stimulation. Further, in vitro kinetic analysis demonstrated that the insulin receptor has a 4-fold greater Vmax with no significant difference in the Km for the purified 52-kDa Shc isoform compared with the 46-kDa Shc isoform. However, the EGF receptor displayed the identical Vmax and Km for tyrosine phosphorylation of both of these species. In direct contrast to the EGF receptor, we also observed significant differences in binding interactions between the insulin receptor with the 52- and 46-kDa Shc isoforms in vitro. These data demonstrate that the predominant insulin-dependent Shc signaling pathway occurs via the 52-kDa Shc isoform, whereas the EGF receptor can effectively use both the 52- and 46-kDa Shc species.

3T3 Cells↗
PubMed1995

Real-time analysis of liposomal trafficking in tumor-bearing mice by use of positron emission tomography.

Long-circulating liposomes are known to accumulate passively in tumor tissues of tumor-bearing animals. To evaluate the in vivo behavior of such liposomes, we investigated the real-time liposomal trafficking by a non-invasive method using position emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, and palmityl-D-glucuronide (PGlcUA) in a molar ratio of 4:4:1 were prepared in the presence of 2-[18F]fluoro-2-deoxyglucose ([2-18F]FDG). [2-18F]FDG-labeled liposomes sized by extrusion through a filter with various-sized pores were administered to mice bearing Meth A sarcoma, and a PET scan was performed for 120 min. Small-sized, long-circulating liposomes (100 nm in diameter) constructed with PGlcUA tended to accumulate in the tumor tissues. On the contrary, control liposomes (100 nm in diameter) containing dipalmitoylphosphatidylglycerol instead of PGlcUA accumulated in the liver. Large-sized PGlcUA-containing liposomes (> 300 nm) also accumulated in the liver, as well as in the spleen. Time-activity curves indicated that the small long-circulating liposomes (< 200 nm) transiently accumulated in the liver right after the injection but that the accumulation there decreased time-dependently. These data suggest that, although the majority of small long-circulating liposomes remain in the bloodstream, some extravasate once into the interstitial spaces in the liver re-enter the bloodstream again, and finally accumulate in the tumor tissues. This PET technique might be useful for studying real-time liposomal trafficking and for tumor imaging.

Animals↗
PubMed1995

Increased permeability of phase-separated liposomal membranes with mixtures of ethanol-induced interdigitated and non-interdigitated structures.

It has been suggested by many workers using model membranes that the interdigitated structure formation, in which the acyl chains fully interpenetrate the hydrocarbon chains of the opposing monolayer, plays an important role in regulating many functions of biomembranes. In the present study the control of permeability was focused on as one of the biomembrane functions, and the effects of ethanol on the permeability of large unilamellar vesicles made by the extrusion technique (LUVET) (average diameter: about 250 nm), composed of dipalmitoyl or egg yolk phosphatidylcholines, were studied by monitoring the leakage of fluorescent dye, calcein, entrapped in the inner aqueous phase of the LUVET. The permeability was estimated from the apparent rate constant of calcein leakage at 25 degrees C. Large permeabilities were observed in the region of 0.6 M to 1.3 M ethanol, with a concentration dependence. In this range of ethanol concentrations the normal bilayer and interdigitated structure coexist and the membrane is in a phase-separated state. The large permeability is due to the instability of the boundary regions, the interdigitated membrane being characterized by a thinner structure and more rigid hydrocarbon regions in the layer than its non-interdigitated counter part. These results suggest the possibility of biomembrane-permeability regulation by interdigitated membrane formation.

Ethanol↗
PubMed1995

Murine spleen stromal cell line SPY3-2 maintains long-term hematopoiesis in vitro.

The hematopoietic microenvironment (HIM) of mouse spleen predominantly induces the differentiation of hematopoietic progenitors into erythroid lineage in vivo. However, the mechanisms of this phenomenon have not been fully explored because of the lack of an adequate in vitro system mimicking the spleen hematopoiesis. To reconstruct the HIM of mouse spleen in vitro, we established spleen stromal cell lines from a three-dimensional (3D) spleen primary culture in collagen gel matrix. Of these, SPY3-2 cells were negative for preadipocytic and endothelial markers, had a fibroblastoid morphology, and were not converted to adipocytes in the presence of 1 mumol/L hydrocortisone. They supported the maintenance and multilineal differentiation of hematopoietic progenitor cells for more than 8 weeks in vitro. The differentiated hematopoietic cells in the coculture medium were predominantly monocytes rather than granulocytes. Furthermore, erythropoiesis was predominantly induced in the presence of 2 U/mL erythropoietin and continued for more than 12 weeks. The number of burst-forming units-erythroid (BFU-E) was increased 10 times after 3 weeks of coculture, which was followed by pronounced production of erythroid cells in the coculture after week 4. SPY3-2 expressed high levels of c-kit ligand and low levels of granulocyte macrophage colony-stimulating factor and interleukin-3, and these molecules were all involved in this long-term erythropoiesis. Thus, the clonal SPY3-2 cell line will provide a novel HIM in vitro analogous to that of mouse spleen in vivo. These results suggest that 3D collagen gel culture may facilitate the establishment of functioning stromal cell lines of hematopoietic organ.

Adipose Tissue↗
PubMed1995

Preconceptional natural-killer-cell activity as a predictor of miscarriage.

There is no immunological test for the prospective identification of alloimmune causes of miscarriage. We investigated whether activity of natural killer cells was predictive of subsequent abortion in women who had had unexplained recurrent abortions and had received no treatment. 24 women with high preconceptional NK activity, defined as mean plus 1 SD of NK activity of 47 controls, had a significantly higher abortion rate in the next pregnancy than 44 women with normal levels of NK activity (71 vs 20%; relative risk 3.5; 95% CI 1.8-6.5). The preconceptional evaluation of NK activity in women with recurrent miscarriages may thus be predictive of the risk of pregnancy loss at the next conception.

Abortion, Habitual↗
PubMed1995

Ethanol-induced aggregation and fusion of small phosphatidylcholine liposome: participation of interdigitated membrane formation in their processes.

The mechanism for the ethanol-induced aggregation/fusion of uniform-sized small liposomes comprised of dipalmitoyl (DPPC) or egg yolk (eggPC) phosphatidylcholines was studied by measuring the average size using a photon correlation spectroscopy, by observing directly the states in the liposomal solutions using freeze-fracture electron microscopy and by attempting resonance energy transfer using flurophore-labeled phospholipids. Abrupt increases in the apparent size of DPPC liposomes were observed in the presence of above 44 mg/ml ethanol, where microscopically plateau membranes form interdigitated structure, in which the acyl chains fully interpenetrate the hydrocarbon chains of the apposing monolayer. On the contrary, in the eggPC liposome, where the membranes cannot form interdigitated structures even in the presence of high concentration of ethanol, such intense aggregation and fusion were not observed, suggesting their intimate relation to the interdigitated structure formation. The formation of interdigitated structures in the adhering region leads to an increase in the interfacial area and an exposure of hydrophobic acyl chain terminal on the surface area, and enhances hydrophobic interactions between two interdigitated bilayers. Thus, the resultant interdigitated structure makes the aggregated state stable and partially initiates the bilayer mixing between the two apposed membranes, leading to fusion.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Characteristic induction of hepatic metallothionein in mice by tumor transplantation.

Based on the previous finding that hepatic metallothionein (MT) level was tumor-growth dependently elevated in tumor-transplanted mice, the mode of induction of hepatic MT in tumor-bearing mice was comparatively studied with inflammation-induced and stress-subjected mice. The prefeeding with zinc (Zn)-deficient diet for 1 wk suppressed both the growth of tumor and the increase of hepatic MT and Zn in tumor-bearing mice. The postfeeding with Zn-deficient diet also suppressed hepatic MT induction in the course of tumor growth. On the other hand, in the other two experimental model mice, the prefeeding with Zn-deficient diet did not suppress the increase of hepatic MT and Zn. Further, the dexamethasone treatment stimulated hepatic MT induction in tumor-bearing mice, but rather reduced that in inflammation-induced mice. These results suggest that hepatic MT was induced uniquely in tumor-bearing mice and that Zn may play a key role for the induction of hepatic MT by tumor transplantation.

Animals↗
PubMed1995

Involvement of preferential formation of apurinic/apyrimidinic sites in dimethylarsenic-induced DNA strand breaks and DNA-protein crosslinks in cultured alveolar epithelial cells.

We previously found that lung-specific DNA damage induced by administration of dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, in mice might be due to dimethylarsenic peroxyl radical [(CH3)2AsOO.] produced in the further metabolic processing of DMAA. Further analysis of DNA damage was performed in the present study using a human embryonic cell line of alveolar epithelial (L-132) cells. Alkali-labile sites in DNA were produced prior to DNA single-strand breaks (SSB) and DNA-protein crosslinks (PC) in L-132 cells by exposure to 10mM DMAA. An experiment using methoxyamine (MA), an agent reacting with the aldehyde group of apurinic/apyrimidinic (AP) sites in DNA, indicated that, of the alkali-labile sites formed by exposure to DMAA, major ones were AP sites. These findings suggest that SSB and PC induced by exposure of L-132 cells to DMAA occurred via the formation of AP sites in DNA. That is, SSB were produced by a beta-elimination reaction on AP sites in the DNA and PC by a Schiff-base reaction between amino groups of nuclear proteins and aldehyde groups of AP sites.

Cacodylic Acid↗
PubMed1995

Intratumoral DNA heterogeneity of small hepatocellular carcinoma.

BACKGROUND: Intratumoral DNA heterogeneity provides important information regarding biologic and clinical behavior. The purpose of this study was to evaluate the incidence of DNA heterogeneity in small hepatocellular carcinoma (HCC) nodules. METHODS: The DNA content of 28 surgically resected small HCC nodules (< or = 3.0 cm) was measured using flow cytometry of fresh or frozen samples taken from different parts of each nodule with reference to the macroscopic features. RESULTS: Of the 28 small HCC nodules, 14 (50.0%) had only DNA diploid stemline characteristics. Five nodules (17.9%) manifested DNA diploid and DNA aneuploidy within the same tumor. Of the remaining nine nodules (32.1%) that showed only DNA aneuploidy, two contained tumor tissues with apparently different DNA content. Thus, DNA heterogeneity was found in 7 (25.0%) of 28 nodules. DNA heterogeneity correlated well with macroscopic histologic features. All four early HCC were composed of only DNA diploid cells, whereas three of six nodule-in-nodule lesions were composed of DNA heterogeneous cells, in which the inner obviously cancerous nodule showed DNA aneuploidy and the outer well differentiated HCC portion demonstrated DNA diploid. Four of 18 overt HCC nodules showed DNA heterogeneity; 2 of these 4 nodules showed both diploid and aneuploid peaks, and the other 2 two showed different aneuploid peaks within the same nodule. CONCLUSIONS: DNA heterogeneity correlating with macroscopic features is found frequently even in small HCC nodules. Therefore, multiple sampling based on macroscopic features is required for the accurate assessment of DNA ploidy, particularly when the information about DNA ploidy is used as a prognostic indicator.

Aged↗
PubMed1995

Leukemic transformation of polycythemia vera and essential thrombocythemia possibly associated with an alkylating agent.

BACKGROUND: Leukemic transformation of polycythemia vera (PV) and essential thrombocythemia (ET) is influenced by the therapeutic modalities used. A high incidence of leukemic transformation was found among patients with PV or ET treated with an alkylating agent, carboquone (CQ). The study was conducted to assess the causal relationship between CQ and leukemic transformation of PV and ET. METHOD: Twenty-seven patients with PV and 29 with ET diagnosed from January 1975 to August 1993 and whose clinical course could be followed comprised the members of this retrospective study. The patients were examined for the treatment administered, hematologic data, vascular complications, malignancies including leukemia, and eventual outcome. RESULTS: Eighteen patients with PV and 16 with ET were treated with CQ. The follow-up was 51-209 months for patients with PV and 28-176 months for those with ET. Three patients with PV (17% of those treated with CQ) and 5 with ET (31% of those treated with CQ) had subsequent transformation to acute leukemia. The median period until transformation of patients with PV was 94 months, whereas the median follow-up of patients without transformation was 146 months (P < 0.01). The median total days of CQ administration and the median total dose of CQ were 2022 days and 1226 mg, respectively, for the patients with transformation and 1051 days (P < 0.05) and 435 mg (P < 0.01), respectively, for those without transformation. Likewise, the median follow-ups for patients with ET with or without transformation were 130 and 90 months, respectively; the difference was insignificant. The median total days of CQ administration and the median total dose of CQ were 2075 days and 1019 mg, respectively, for patients with transformation and 571 days (P < 0.05) and 231 mg (P < 0.01), respectively, for those without transformation. These observations suggest that CQ may be involved in the leukemic transformation of PV and ET. The subtypes of leukemia transformed from PV corresponded to M2 in two patients and to M4 in one. All five patients with ET were found to have megakaryoblastic features at transformation, and three were diagnosed as having leukemic subtype M7. Chromosomal abnormalities were found in all five patients (two PV and three ET) examined after leukemic transformation, showing multiple and complex abnormalities in four. CONCLUSION: Showing that both the total days of CQ administration and the total dose of CQ were larger for patients with PV or ET whose disease subsequently transformed to leukemia, with this study, a possible causal role of CQ in leukemic transformation of PV and ET is suggested.

Adult↗
PubMed1995

Interaction between valproate formulation and phenytoin concentrations.

Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was replaced by the same dose as a slow-release tablet. The mean plasma phenytoin level rose significantly from 14.4 to 18.7 micrograms.ml-1. Nine of eleven patients had markedly increased phenytoin levels (by 21 to 72%), and two developed toxic symptoms. The results indicate that changing valproate formulations can cause major alterations in the plasma concentration of co-administered phenytoin.

Adolescent↗
PubMed1995

Renal cysts and associated renal tumours in male ddY mice injected with ferric nitrilotriacetate.

In experiments using ferric nitrilotriacetate (Fe-NTA) as a renal carcinogen, multiple renal cysts are often observed in addition to renal tumours. In the present study, we used 3-week-old male ddY mice and examined the relation between renal cysts and cancer development. Four months after the start of Fe-NTA administration, we observed cysts in the renal cortex in all Fe-NTA-treated mice, but not in Fe-free NTA-treated mice. Three types of cysts were observed, but only those which originated from the renal proximal tubules showed multilayered or papillary growth of cyst epithelial cells. Using histochemical staining, we found a cyst formation-tumour induction sequence, and the supposed cystic-papillary tumour induced by Fe-NTA was of proximal tubular cell origin. We also found that the minimum dose of Fe-NTA capable of inducing renal tumours in ddY mice was 10 mg of iron/kg/day, four times in 2 weeks.

Animals↗
PubMed1995

Surgical treatment of an enormous aneurysmal portahepatic venous fistula: report of a case.

We report herein the case of a 20-year-old woman in whom an enormous aneurysmal portahepatic venous fistula was found. The portal aneurysm developed in the anterior inferior segment of the right hepatic lobe, and communicated with the right portal vein and the right hepatic vein. Due to the enormous size of the shunt, and because the patient's venous blood ammonia level increased by about twofold after eating, a right lobectomy of the liver was performed. A review of the available literature and a discussion of the most appropriate treatment follows the presentation of this case.

Adolescent↗
PubMed1995

High affinity IgE receptor (Fc epsilon RI) expression on eosinophils infiltrating the lesions and mite patch tested sites in atopic dermatitis.

Expression of the high affinity IgE receptor (Fc epsilon RI) on eosinophils has recently been reported. This led us to evaluate Fc epsilon RI expression on eosinophils in atopic dermatitis (AD). Double immunofluorescence stainings with an anti-Fc epsilon RI monoclonal antibody (mAb) and a polyclonal antieosinophil cationic protein (ECP) antibody were performed on lesional biopsy specimens from patients with AD and from patients with bullous pemphigoid (BP) as controls. In AD and BP lesions, 77% and 70% of eosinophils expressed Fc epsilon RI, respectively. However, the intensity of Fc epsilon RI staining in AD was much stronger than in BP, suggesting upregulation of Fc epsilon RI expression on eosinophils in AD. In addition, the eosinophils infiltrating AD lesions were stained strongly with anti-CD23 mAb and anti-IgE antibody. At the sites of mite patch testing in AD, Fc epsilon RI-, CD23- and IgE-positive eosinophils were observed to the same degree as in the lesions, and a considerable number of mite antigen-bearing eosinophils were detected. Fc epsilon RI and CD23 were both upregulated on the skin-infiltrating eosinophils in AD and bound IgE molecules.

Adult↗