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Biomedical subjects

M Okamura

Publications and source records attributed to M Okamura.

At least 73 records · Page 4Linked to original sources
PubMed1995

[An autopsy case of immature teratoma with choriocarcinoma in the mediastinum].

The autopsy of a 28-year-old Japanese male patient, which revealed immature teratoma combined with choriocarcinoma in the mediastinum, is presented. The tumor, which was removed after chemotherapy, was localized in the superior-anterior mediastinum. Chemotherapy was performed several times after operation. However, HCG increased again, and a roentgenogram revealed metastatic shadows in both lungs. The metastatic tumors in the lungs showed only the choriocarcinoma.

Adult↗
PubMed1994

Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor gene expression in aortic smooth muscle cells of spontaneously hypertensive rats.

To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.

Animals↗
PubMed1994

A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: effects of particle size and dose on chitin-containing cis-diamminedichloroplatinum(II) albumin microsphere antitumor activity in VX2 hepatic tumor model rabbits.

We prepared chitin-containing cis-diamminedichloroplatinum(II) (CDDP) albumin microspheres with various particle sizes, and investigated in vitro CDDP release; the antitumor effect towards VX2 tumor introduced into rabbits was then examined. It was found that the rate of release of CDDP from chitin-containing CDDP albumin microspheres in vitro was increased with reduced particle size. Administration of microspheres to VX2 tumor-bearing rabbits via the hepatic artery resulted in different profiles of plasma platinum concentration depending on the particle size, and a higher concentration of platinum was released from the beginning of administration as particle size was reduced. The platinum content in hepatic tissue following the administration of CDDP microspheres was increased as the particle size decreased, although the rate of increase was not uniform. The antitumor effect of CDDP assessed by the suppression of tumor growth tended to be higher when microspheres of smaller sizes were used. However, no significant difference was observed in tumor growth rate between rabbits injected with microspheres smaller than 20 microns and those injected with sizes between 20 and 37 microns (p > 0.05). We also examined the relationship between the CDDP dose and antitumor effect using microspheres of less than 20 microns and observed a dose-dependent antitumor effect. No significant difference was observed, however, between 2 and 4 mg eq CDDP/kg dose levels (p > 0.05). From these results, we concluded that microsphere size and CDDP dose were strongly correlated with the augmentation of antitumor effect of chitin-containing CDDP albumin microspheres used in chemo-embolization therapy via the hepatic artery.

Albumins↗
PubMed1994

Distribution of ascorbic acid analogs and associated glycosides in mushrooms.

Mushrooms contain reducing substances with chemical properties similar to ascorbic acid (AsA). In this study, the four types of reducing substances contained in Flammulina velutipes (Enokitake), Hypsizigus mamoreus (Bunashimeji), Pholiota nameko (Nameko), and Grifola frondosa (Maitake) were respectively purified, and the structure of each was analyzed using nuclear magnetic resonance (NMR) and other methods. The results confirmed that those substances were AsA analogs and associated glycosides (6-deoxy-AsA, 6-deoxy-5-O-(alpha-D-xylopyranosyl)-AsA, 6-deoxy-5-O-(alpha-D-glucopyranosyl)-AsA, and 5-O-alpha-D-glucopyranosyl-erythro-AsA). These substances were characteristic in that saccharide was bonded with the C-5 of the AsA analogs. Osazones were formed from the reducing substances in 19 kinds of edible mushrooms. Using thin-layer chromatography (TLC), they were developed to examine the distribution of the above reducing substances and AsA. The results showed that at least one of the above compounds was certain to be present in any mushroom; that AsA was present in very small quantities if at all; and that several substances similar to the above compounds were present.

Ascorbic Acid↗
PubMed1994

Human P-glycoprotein as a multi-drug transporter analyzed by using transepithelial transport system.

To analyze the mechanism of drug transport, mechanism of inhibitors, and physiological substrates of human P-glycoprotein, we established a transepithelial transport system by introducing MDR1 cDNA into LLC-PK1, a pig kidney epithelial cell line. P-glycoprotein functions as a steroid transporter as well as a drug transporter as physiological functions. P-glycoprotein also transports MDR modulators such as cyclosporin A, FK506, and calcium channel blockers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Anti-Ro/SS-A antibody-positive interstitial pneumonitis in a non-lupus patient.

We describe a 42-year-old anti-Ro/SS-A antibody positive non-lupus patient who developed interstitial pneumonitis in combination with several common clinical features with previously reported lupus pneumonitis patients whose anti-Ro/SS-A antibodies were positive, while whose antinuclear antibodies were negative. We consider that these patients may belong to a same new clinical entity. A variety of characteristic manifestations related to anti-Ro/SS-A antibodies has been reported in patients with systemic lupus erythematosus (SLE) and other connective tissue diseases [1] [2], and an association between these antibodies with pulmonary parenchymal involvement has been reported by Hedgpeth and Boulware in patients with SLE [3] [4]. We report here a 42-year-old non-lupus male patient with pulmonary fibrosis who presented with anti-Ro/SS-A antibodies.

Adult↗
PubMed1994

Modulation of protein kinase C in aorta of spontaneously hypertensive rats with enalapril treatment.

We measured protein kinase C (PKC) activity, levels of PKC alpha enzyme and PKC alpha mRNA in aortic media of spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto rats (WKY) and enalapril treated SHR (enal-SHR) to examine whether hypotensive treatment of enalapril modulates PKC in aortic media of SHR. The cytosolic PKC activity in crude samples of aortic media of SHR was higher than in those of WKY or enal-SHR (p < 0.01) and was closely associated with blood pressure (r = 0.84, p < 0.001). The membrane PKC activity was detected in samples of SHR, but virtually no activity was detected in samples of WKY or enal-SHR. The cytosolic PKC activity in DEAE column purified samples of SHR was also higher than in those of WKY or enal-SHR (p < 0.01). The PKC alpha enzyme levels (74-kDa and 77-kDa protein) detected by immunoblot were higher in SHR than in WKY or enal-SHR (p < 0.01). The mRNA levels of PKC alpha were higher in SHR than in WKY (p < 0.01) and were much decreased in enal-SHR (p < 0.01). Thus, PKC activity, PKC alpha and its mRNA levels were higher in aortic media of SHR than those in WKY and these increased levels were reversed with enalapril treatment. Considering the pivotal roles of PKC in the mechanism of cellular proliferation and the pathogenesis of hypertension, these results provide clues in understanding the pathogenesis of hypertension, mechanisms of vascular hypertrophy in hypertension and the beneficial effects of angiotensin converting enzyme inhibitor in the treatment of hypertension.

Animals↗
PubMed1994

Enhancement of hypertension and renal injury by salt-loading during chronic nitric oxide inhibition. Effects of TCV-116, a novel angiotensin II receptor antagonist.

Endothelium-derived nitric oxide (EDNO) and angiotensin II play a role in the regulation of vascular tone and sodium handling. The objective of this study was to determine the role played by angiotensin II in mediating the arterial pressure and renal response to increments in sodium intake during chronic EDNO inhibition. Six groups of Wistar rats were studied; they were fed either a normal sodium diet (groups I, II, and III) or a high sodium diet (groups IV, V and VI). Rats in groups II, III, V and VI were placed on oral L-N-nitroarginine-methyl ester (L-NAME) for 4 weeks. In groups III and VI, the angiotensin II receptor antagonist, TCV-116, was administered. A significant increase in blood pressure was observed in group V compared with group II at the end of the experimental period. TCV-116 attenuated the L-NAME-induced hypertension in both group III and group VI. Urinary protein excretion and the glomerular sclerotic injury score in group V were greater than in group II. TCV-116 attenuated the proteinuria and glomerular injury induced by chronic EDNO inhibition in the groups with normal (group III) and high sodium intake (group IV). Systemic hypertension and glomerular injury were enhanced by salt loading during EDNO inhibition, and the angiotensin II receptor antagonist, TCV-116, attenuated this salt-induced increase in blood pressure and renal injury, suggesting that EDNO may counteract the renal effects of angiotensin II.

Angiotensin Receptor Antagonists↗
PubMed1994

p-Aminohippurate transport in apical and basolateral membranes of the OK kidney epithelial cells.

p-Aminohippurate (PAH) transport in apical and basolateral membranes of OK cells was studied to characterize each membrane process and to determine which process is important for the vectorial transport of PAH across the OK cell monolayers. PAH uptake from the basal side into OK cells was much higher than from the apical side, and was inhibited almost completely by anion transport inhibitors (probenecid and furosemide) and low temperature. On the other hand, PAH efflux from OK cells to the apical side was higher than to the basal side. The efflux across the apical membrane also was inhibited by the transport inhibitors and low temperature. The uptake of PAH across the basolateral membrane was inhibited by dicarboxylates such as alpha-ketoglutarate, and kinetic analysis showed that the inhibition was a mixed-type. These findings suggest that PAH transport in apical and basolateral membranes of OK cells is a specifically mediated process, and both processes contribute to the vectorial transport of PAH across the cell monolayers. PAH/dicarboxylate exchange may be involved in PAH transport in the basolateral membrane of OK cells.

Animals↗
PubMed1993

Increased endothelial gene expression of angiotensin AT1A receptor in cyclosporine induced hypertensive rats.

We examined the gene expression of angiotensin AT1A receptors in aortic endothelial cells of cyclosporine induced hypertensive rats using reverse transcribed polymerase chain reaction method. The gene expression of angiotensin AT1A receptors in aortic endothelial cells of cyclosporine induced hypertensive rats showed a two-fold increase when compared with that in normotensive control rats. These results raise a possibility that the up-regulation of endothelial angiotensin AT1A receptors participates in the pathogenesis of cyclosporine induced hypertension.

Angiotensin I↗
PubMed1993

Immunohistochemical demonstration of protein gene product 9.5 (PGP 9.5) in the primary olfactory system of the rat.

Immunohistochemical localization of protein gene product 9.5 (PGP 9.5) was examined in the primary olfactory system of the rat. Receptor cells were intensely immunopositive in the olfactory epithelium, vomeronasal organ and septal olfactory organ of Masara. The mitral cells and some of the short-axon cells of the main olfactory bulb (MOB) were also intensely immunopositive, while the tufted cells of the MOB and the mitral/tufted cells of the accessory olfactory bulb varied in immunoreactivity.

Animals↗
PubMed1993

Westernized food habits and concentrations of serum lipids in the Japanese.

To investigate the association of westernized food habits and concentrations of serum lipids in the Japanese, we studied 1200 healthy Japanese living in Hiroshima prefecture and 1483 ethnic Japanese from Hiroshima prefecture living in the Hawaii Islands and Los Angeles. The nutritional assessments were made by the same dietitians. No major difference was observed in the total energy intake between the Japanese and the Japanese-Americans in both males and females. However, the intake of animal fat and simple carbohydrates (especially fructose) were markedly greater, and that of complex carbohydrates lower, in the Japanese-Americans compared with the Japanese. The mean serum cholesterol (CH), LDL-CH and serum triglyceride (TG) levels were significantly higher in the Japanese-Americans in both sexes. The mean HDL-CH concentration was similar between the two groups in males, but it was approximately 7 mg/dl higher in Japanese-American females. Using the 75 percentile values of CH and TG in the Japanese in Hiroshima, the frequency of WHO types IIa and IIb hyperlipidemia was about twice as high in the Japanese-Americans. These results suggest that westernized food habits in the Japanese include qualitative changes in animal fat, simple carbohydrate and complex carbohydrate diet rather than an increase in the total energy intake. These changes are associated with marked increases in the concentrations of serum CH and TG and increased prevalence of types IIa and IIb hyperlipidemia.

Adult↗
PubMed1993

Significance of enzyme linked immunosorbent assay (ELISA) for antibodies to double stranded and single stranded DNA in patients with lupus nephritis: correlation with severity of renal histology.

The correlation between renal histology and class specific (IgG and IgM) antibodies to double stranded DNA (dsDNA) and single stranded DNA (ssDNA) was studied by enzyme linked immunosorbent assay (ELISA) in 40 untreated patients with systemic lupus erythematosus (SLE). The levels of IgG antibodies to dsDNA were significantly higher in patients with World Health Organisation class IV nephritis than in those with class I, class II, or class III nephritis. IgG antibodies to ssDNA were higher in patients with class IV than in those with class II nephritis. IgG antibodies to dsDNA showed a close correlation with the histological activity score and the amount of electron dense deposit. IgG antibodies to ssDNA showed only a weak correlation with the renal histological activity score. IgM antibodies to dsDNA and IgM antibodies to ssDNA were not correlated with renal histological features. Patients with moderate to severe nephritis had a lower ratio of IgM antibodies to dsDNA to IgG antibodies to dsDNA than those with mild nephritis. These results indicate that the measurement of IgG antibodies to dsDNA is predictive in evaluating renal histological activity in patients with SLE.

Antibodies, Antinuclear↗
PubMed1993

Transport of organic anion in the OK kidney epithelial cell line.

Transport of an organic anion, p-aminohippurate (PAH), was investigated in an established cell line derived from the American opossum kidney (OK). Transepithelial transport and accumulation of PAH were measured in OK cells cultured on permeable supports. Specifically mediated transcellular transport of PAH across OK cell monolayers occurred only from basal to apical side, and the accumulation of PAH in the cells was much larger from basal side than from apical side. Both the transcellular transport of PAH from basal to apical side and the accumulation from basal side were temperature dependent, saturable, and inhibited by organic anions such as probenecid but not by organic cations. In contrast, such a specific transport of PAH was not observed in LLC-PK1, another epithelial cell line derived from pig kidney. These findings suggest that OK cells can transport PAH by the organic anion transport system unidirectionally from basal to apical side across the cell monolayers and that OK cells might be a useful model for the study of organic anion secretion in the renal proximal tubules.

Animals↗
PubMed1993

A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: effects of chitin concentration on cis-diamminedichloroplatinum(II) albumin microsphere properties and antitumor effect in VX2 hepatocellular carcinoma model rabbits.

cis-Diamminedichloroplatinum(II) (CDDP) albumin microspheres were prepared with various chitin concentrations and microsphere CDDP contents, specific surface area, surface structure and other microsphere properties. CDDP release in vitro and the antitumor effect in VX2 tumor model rabbits were investigated. CDDP content was increased as the concentration of chitin increased; at a chitin concentration of 6.0% it was about 2 times that without chitin. Specific surface area also increased with chitin concentration. CDDP release rate from various microspheres in vitro was suppressed as chitin concentration increased. Thus, microsphere properties, especially surface structure, are affected by an increase in chitin concentration. In experiments in vivo, various microspheres were injected into the hepatic artery of VX2 hepatocellular carcinoma model rabbits, and the effects of the chitin concentration on the time course of blood platinum (Pt) level and the antitumor effect were assessed. The blood Pt concentration increased with increase in chitin concentration, with a maximum of 0.45 microgram/ml at a concentration of 6.0%, even 7 d following microsphere administration. Tumor growth was suppressed when the chitin concentration was increased. Tissue Pt concentrations also increased in the presence of chitin. These findings suggest that increasing the chitin concentration might promote microsphere decomposition and hence CDDP release in vivo, thus improving immunopotentiating activity and resulting in enhanced CDDP antitumor effect. The detailed mechanisms of the action, however remains to be studied.

Albumins↗
PubMed1993

Vitamin E is an important factor in T cell differentiation in thymus of F344 rats.

The effect of vitamin E (dl-alpha-tocopheryl acetate) on T cell differentiation in thymus of F344 rats was examined in this study. The rats were divided into three groups: vitamin E-free, regular and high vitamin E groups and fed a diet containing various levels of vitamin E (0, 50, and 585 mg/kg diet) for 7 weeks. The number of thymocytes was significantly lower in the vitamin E-free group relative to the regular group. Although the proportions of both CD4+CD8- and CD4-CD8+ T cells in thymocytes were significantly greater in the high vitamin E group, the proportion of CD4+CD8- T cells inversely decreased in vitamin E-free group compared to that of the regular group. The ratio of CD4+CD8-/CD4-CD8+ T cells increased in the high vitamin E group (p < 0.01) and significantly decreased in the vitamin E-free group (p < 0.001) compared to that of the regular group. Although the marked changes of T cell subsets were not seen in peripheral blood lymphocytes (PBL), the ratio of CD4+CD8-/CD4-CD8+ T cells was significantly lower in the vitamin E-free group and significantly greater in the high vitamin E group compared to that of the regular group. Production of interleukin (IL) 2 by thymocytes following the stimulation with Con A for 48 h increased about threefold in the high vitamin E group compared to the regular group. Conversely, thymocytes from rats fed the vitamin E-free diet showed a significant decrease of IL2 production compared to that of the regular group. Prostaglandin E2 (PGE2) production from thymocytes was significantly lower in the high vitamin E group compared to that of the regular group, whereas thymocytes of rats fed the vitamin E-free diet showed a significant increase of PGE2 production compared to that of rats fed the regular diet. Furthermore, in vitro addition of indomethacin provided a restoration of IL2 production from thymocytes of rats fed the vitamin E-free diet to the level of rats fed the regular diet. These results suggest that vitamin E plays an important role in T cell differentiation in thymus, which may be related to the action of vitamin E as antioxidant.

Animals↗