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Biomedical subjects

S Oikawa

Publications and source records attributed to S Oikawa.

At least 199 records · Page 11Linked to original sources

Effect of orally administered beta-glucan on macrophage function in mice.

The effect of orally administered SSG, a beta-1,3-glucan obtained from the culture filtrate of the fungus Sclerotinia sclerotiorum IFO 9395, on the function of peritoneal macrophages in CDF1 mice was examined. Oral administration of SSG (20, 40, 80 or 160 mg/kg, daily for 10 consecutive days) enhanced the acid phosphatase activity of peritoneal macrophages. The greatest enhancing effect was observed at 80 mg/kg of SSG. Relatively long periods of administration (more than 10 consecutive days) were needed to induce significant enhancing effects. Phagocytic activity, candidacidal activity, hydrogen peroxide (H2O2) production and interleukin-1 (IL-1) production of peritoneal macrophages were also enhanced after the administration of SSG by the oral route (80 or 160 mg/kg). However, the durations of the activated state after completion of administration differed depending on the activity. Enhanced activity of lysosomal enzyme (acid phosphatase) was also shown in peritoneal macrophages taken from C3H/HeJ mice, which is a nonresponder strain to bacterial lipopolysaccharide (LPS). These results demonstrate that SSG given by the oral route can activate peritoneal macrophages in mice.

Adjuvants, Immunologic↗

Changes of atrial natriuretic peptide and its messenger RNA with development and regression of cardiac hypertrophy in renovascular hypertensive rats.

We assessed the changes in atrial natriuretic peptide (ANP) and its messenger RNA (mRNA) levels in atria and ventricles in relation to hemodynamic factors during antihypertensive treatments in two-kidney, one-clip renovascular hypertensive rats (RHRs). Hypertension of 10-week duration caused a twofold increase in the left ventricular weight/body weight ratio, a significant increase in left ventricular end-diastolic pressure, and an eightfold increase in left ventricular ANP mRNA levels in RHRs, as compared with the levels in control rats. Uninephrectomy or 4 weeks of treatment with the converting enzyme inhibitor enalapril reduced the blood pressure to the control level, with the complete reversal of left ventricular hypertrophy, left ventricular end-diastolic pressure, and ANP mRNA levels. Four weeks of treatment with the arterial vasodilator hydralazine significantly, but not completely, reduced the high blood pressure, but it did not influence left ventricular hypertrophy, end-diastolic pressure, and ANP mRNA levels. The increased ANP synthesis observed in the right ventricles of RHRs also reverted to the control level by uninephrectomy or enalapril treatment, but not by hydralazine, with a time course similar to that of left ventricular ANP. In addition, uninephrectomy caused the left and right ventricular ANP and ANP mRNA levels of RHRs to fall to the levels of control rats as early as 1 week, despite persistent left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stimulation of rat atrial natriuretic peptide (rANP) synthesis by triiodothyronine and thyroxine (T4): T4 as a prohormone in synthesizing rANP.

Thyroid hormones have been reported to increase the secretion and synthesis of atrial natriuretic peptide (ANP) in vitro. In this study, we focused on the role of type I T4 5'-deiodinase to investigate the stimulating effects of T4 on ANP synthesis and secretion by measuring cellular content and secretion into the medium of immunoreactive rat ANP (IR-rANP) and rANP mRNA levels in cultured rat neonatal atrial myocytes. Both T3 (10(-9)-10(-7) M) and T4 (10(-8)-10(-6) M) increased cellular content and secretion into the medium of IR-rANP in a dose-dependent manner. However, these effects of T4 were completely inhibited by the addition of propylthiouracil, which selectively suppressed type I T4 5'-deiodinase activity. Methimazole, which did not alter T4 5'-deiodinase activity, had no effects on T4-induced IR-rANP increase. In the measurements of rANP mRNA levels by dot blot analysis, T3 (10(-8) and 10(-7) M) and T4 (10(-7) and 10(-6) M) increased rANP mRNA levels in the same way as they increased IR-rANP content. Although T4-increased rANP mRNA levels were also inhibited by propylthiouracil, methimazole did not alter the effect of T4. Moreover, T4-induced rANP mRNA accumulation in atrial myocytes was further stimulated by the addition of dithiothreitol, suggesting that the deiodinating activity was thiol sensitive. These data suggest that the stimulating effect of T4 on cellular IR-rANP content and rANP mRNA levels is entirely induced after it is converted to T3 by type I T4 5'-deiodinase in atrial myocytes and that T4 serves as a prohormone for T3 in synthesizing rANP.

Animals↗

Enhancement of hematopoietic response of mice by intraperitoneal administration of a beta-glucan, SSG, obtained from Sclerotinia sclerotiorum.

Effects of intraperitoneal (i.p.) administration of SSG, a (1----3)-beta-D-glucan obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, on hematopoietic responses of mice were investigated. Numbers of spleen and peripheral leukocytes increased 7 d after administration of SSG (250 micrograms/mouse). The percentages of polymorphonuclear leukocytes (PMN) in both spleen and peripheral blood increased markedly. The numbers of macrophage progenitor cells also increased in both spleens and femurs of the mice administered SSG. Furthermore, levels of colony-stimulating activity (CSA) in sera were elevated, and two peaks were observed (at 6 h and on day 7 after administration). Elevated CSAs were also observed in the cultures of peritoneal cells taken from mice 3 or 6 h after administration of SSG. These results may suggest that i.p. administration of SSG into mice enhanced the production of colony-stimulating factors (CSFs), and then increased the numbers of both spleen and peripheral blood leukocytes.

Animals↗

Change of biological activities of (1----3)-beta-D-glucan from Grifola frondosa upon molecular weight reduction by heat treatment.

Changes of biological activities manifested by (1----6)-branched (1----3)-beta-D-glucans of various molecular weights obtained by heat treatment of the corresponding intact beta-glucan at 150 degrees C (HD-LE) were examined. The activities assessed in this study were as follows: an antitumor activity, activation of alternative complement pathway, glucose consumption by macrophages, macrophage-mediated lysosomal enzyme activity in culture supernatant and cell lysate, interleukin-1 (IL-1) activity, and adjuvant activity. HD-LE could be classified into three groups: 1) HD-LE 0 h (MW 800000) which activated all of the biological activities tested, 2) HD-LE 0.5 and 3 h (MW 250000 and 21000) which lacked or exhibited low levels of activities such as activation of alternative complement pathway and lysosomal enzyme secretion, 3) HD-LE 6 h (MW 6400) which only activated glucose consumption and synthesis of lysosomal enzyme. These results suggest that an antitumor glucan is not always a multiple enhancer of host defense mechanisms and that a large molecular weight is required to augment multiple immunological activities.

Animals↗

Macrophage activation in vitro by chemically cross-linked (1----3)-beta-D-glucans.

The chemical cross-linking of soluble (1----3)-beta-D-glucans having molecular weights of 21000 (CL 3 h) and 6400 (CL 6 h), and laminarin (CL LAMI), which showed negligible biological activity, by epichlorohydrin provided rigid particles. These particles showed no gel-to-sol transition upon the addition of sodium hydroxide. We compared the effects of chemical cross-linking on the biological activities of glucans. The alternative complement pathway was not activated by any of the cross-linked glucans. Glucose consumption, lysosomal enzyme release, and interleukin-1 production by mouse resident peritoneal macrophages incubated in vitro were strongly induced by CL 3 h, CL 6 h and CL LAMI. However, cross-linked dextran, Sephadex, did not exhibit any of these biological activities. These results suggested that chemical cross-linking of (1----3)-beta-D-glucans enhances macrophage activities without opsonization by complement components.

Animals↗

Absence of angiogenesis-inhibitory activity in aqueous humor of diabetic rabbits.

We studied inhibitory activity of angiogenesis in the eye to explore the formation of new blood vessels in diabetic microvascular diseases. When we examined the effects of extracts from various ocular tissues of nondiabetic rabbits on the proliferation of bovine aortic endothelial cells, potent inhibitory activity was found in lens and aqueous humor. Aqueous humor inhibited both angiogenesis on chorioallantoic membrane in vivo and promotion of endothelial cell growth in vitro, which were induced by retinal extracts. However, in diabetic rabbits, aqueous humor lost the ability to inhibit the growth of endothelial cells. The loss of activity became evident 1 mo after the alloxan injection and lasted while the animals were hyperglycemic. In addition, diabetic aqueous humor failed to suppress retinal extract-induced angiogenesis promotion and endothelial cell growth. The absence of the inhibitory activity of angiogenesis in diabetic aqueous humor might be involved in promotion of neovascularization in diabetic ocular disease.

Allantois↗

Endothelin stimulates accumulations of cellular atrial natriuretic peptide and its messenger RNA in rat cardiocytes.

The effect of endothelin-1 (ET-1) on secretion and synthesis of rat atrial natriuretic peptide (rANP) as well as its mRNA levels was studied in primary cultures of neonatal rat atrial cardiocytes. ET-1 dose-dependently (10(-10)-10(-7) M) increased media and cellular rANP-like immunoreactivity as well as its cytoplasmic mRNA levels in rat cardiocytes during 24 hrs incubation. These results suggest that ET-1 directly stimulates expression of the rANP gene in cardiocytes, thereby leading to enhanced synthesis and secretion of rANP.

Animals↗

Cell adhesion activity of non-specific cross-reacting antigen (NCA) and carcinoembryonic antigen (CEA) expressed on CHO cell surface: homophilic and heterophilic adhesion.

Cell adhesion activity of carcinoembryonic antigen (CEA) and non-specific cross-reacting antigen (NCA) has been analysed by using CHO cells which had been transfected with cDNAs and are ectopically expressing each antigen on their surface. CEA expressing CHO tended to aggregate easily within 30 min after being suspended by trypsinization. Cell adhesion assay between 51Cr labelled cells and monolayered cells showed both homophilic and heterophilic interaction, the extent of which was CEA-CEA much greater than CEA-NCA greater than NCA-NCA. These reactions were completely inhibited by Fab' fragment of anti-CEA antibody. The results strongly suggested that CEA and NCA function as Ca++ independent cell adhesion molecules by homophilic and heterophilic interactions.

Animals↗

A pregnancy-specific beta 1-glycoprotein, a CEA gene family member, expressed in a human promyelocytic leukemia cell line, HL-60: structures of protein, mRNA and gene.

Both genomic and cDNA clones encoding a precursor for a pregnancy-specific beta 1-glycoprotein (PS beta G) belonging to the CEA family, expressed in a human promyelocytic leukemia cell line, HL-60, have been isolated and the entire primary structure of the precursor is deduced. The 335-AA precursor has a 34-AA signal peptide followed by domains of N, IIA, IIB and C, which are encoded by separate exons. The genomic sequence contains extra exons IA and IB between exons N and IIA. Apparently, exon IA is excluded from the mRNA by alternative splicing while IB is a pseudo-exon having a stop codon formed by a deletion of dinucleotide in the middle of the sequence. This provides another mechanism to render exon IB abortive and is different from that we reported for another PS beta G (Biochem. Biophys. Res. Comm. (1988) 156, 68-77).

Amino Acid Sequence↗

Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type IIa hyperlipoproteinemia.

The purpose of the present study is to elucidate the characteristics of lipoprotein disorders in diabetes mellitus. By analytical ultracentrifugation, non-insulin-dependent diabetic patients (NIDDM) with type IIa hyperlipoproteinemia (HLP) showed significantly higher incidence of multidisperse low density lipoprotein (LDL) than non-diabetics with type IIa HLP. Furthermore, LDL multidispersity in diabetic subjects seemed to be directly related to neither triglyceride (TG) levels in very low density lipoprotein (VLDL) nor the degree of glycemic control. Diabetics with multidisperse LDL had a lipoprotein profile that was different from the subjects with paucidisperse LDL as follows: (1) enrichment in the cholesterol content of VLDL, (2) TG-rich LDL with small flotation coefficient, (3) low cholesterol levels in high density lipoprotein2 along with enrichment in TG, and (4) high plasma concentrations of apoprotein B. Although the underlying mechanism behind the prevalence of multidisperse LDL in NIDDM with type IIa HLP remains unknown, it seems important that lipoprotein disorders in diabetics with multidisperse LDL were potentially atherogenic.

Aged↗

Lipoprotein glomerulopathy: glomerular lipoprotein thrombi in a patient with hyperlipoproteinemia.

An unusual nephropathy presumably induced by abnormal lipid metabolism is described in a 57-year-old woman who presented with proteinuria and edema. Histology at renal biopsy was characterized by marked dilatation of capillary lumina. Sudan staining and electron microscopy demonstrated lipid droplets occupying the capillary lumina. The patient had no particular clinical symptoms of lipidosis, but hyperlipoproteinemia similar to type III was suggested by lipid profiles. The nephropathy is thought to be an inherited disorder because proteinuria was detected in her sisters and similar renal histology and lipid profile were observed in one of her sisters. This is believed to be the first detailed report of glomerular lipoprotein thrombi.

Adult↗

A novel acid phosphatase excreted by Penicillium funiculosum that hydrolyzes both phosphodiesters and phosphomonoesters with aryl leaving groups.

An acid phosphatase has been purified from the culture broth of Penicillium funiculosum by procedures including SP-Sephadex column chromatography and Sephacryl S-200 gel filtration. The phosphatase appears to be a 76 kDa heterodimer composed of 51 and 26 kDa subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme hydrolyzes both phosphodiesters and phosphomonoesters, but only those with aryl leaving groups. At the early phase of degradation of bis-p-nitrophenyl phosphate by the enzyme, inorganic phosphate and the intermediary product, p-nitrophenyl phosphate, are liberated at approximately the same rate. This indicates that the intermediary phosphomonoester produced on the enzyme is further hydrolyzed in situ or dissociates into the medium at approximately the same probability.

Acid Phosphatase↗

Multicentric astrocytomas of the optic chiasm, brain stem and spinal cord.

Autopsy was performed on a 52-year-old man with a 20-year history of neurological symptoms. At autopsy, both a brain stem tumor and a spinal cord tumor were found. These showed the features of pilocytic astrocytoma histologically. A pilocytic astrocytoma was also found in the optic chiasm upon microscopical examination. These three tumors were thought to be multicentric astrocytomas, because there was no continuity among them and no evidence of dissemination or metastasis by any pathway. From a review of the literature, the present case is considered to be an exceedingly rare one because of the multicentric sites of occurrence.

Adult↗

Regional assignment of nonspecific cross-reacting antigen (NCA) of the CEA gene family to chromosome 19 at band q13.2.

Nonspecific cross-reacting antigen (NCA) is a member of the carcinoembryonic antigen (CEA) gene family. Recently, a DNA segment for part of the human NCA gene was isolated and sequenced. We mapped this gene by Southern blot analysis of hybrid cells and by in situ hybridization. The Southern blot analysis indicated that the NCA gene is on human chromosome 19 and the in situ hybridizations localized the gene to band 19q13.2.

Animals↗

Modulation of antitumor activity of grifolan by subsequent administration of (1----3)-beta-D-glucanase in vivo.

The initiation process of effector mechanism of the antitumor activity of (1----3)-beta-D-glucans has been examined in detail by applying treatment of mice with (1----3)-beta-D-glucanase, kitalase (KIT) and zymolyase (ZYM), via i.p. route after i.p. administration of (1----3)-beta-D-glucans, grifolan (GRN) and CM-curdlan (CM-CUD). A significant decrease of antitumor activity caused by GRN was observed by treatment with KIT within 48 h, and that caused by GRN administered via i.v. route was also reduced by the i.v. injection of KIT, although it was less effective than i.p. treatment. Pretreatment of mice with thioglycollate reduced the period of time to abrogate antitumor activity by the sequential treatment of KIT. Similar results were also observed on ZYM treatment after i.p. treatment of CM-CUD. These facts suggest that the period of manifestation of the antitumor activity by (1----3)-beta-D-glucans must be longer than a few days.

Adjuvants, Immunologic↗

Modification of immunostimulating activities of grifolan by the treatment with (1----3)-beta-D-glucanase.

We have developed a method to control the effective time period of (1----3)-beta-D-glucan in vivo by using (1----3)-beta-D-glucanase and found that grifolan LE (GRN), a (1----3)-beta-D-glucan, administered intraperitoneally to the host required more than 2 d to exert antitumor activity. During these two days many immunological changes were induced, such as increasing the number of peritoneal exudated cells (PEC), augmentation of production of interleukin 1 (IL-1), acid phosphatase and phagocytic capacity of adherent cells in PEC. In addition, there was increased carbon clearance activity in vivo, augmentation of responsiveness of splenocytes to mitogens such as concanavalin A and lipopolysaccharide (LPS) and production of ceruloplasmin. When (1----3)-beta-D-glucanase was injected 1 d after GRN administration, IL-1 productivity and responsiveness to LPS were significantly reduced, but lysosomal enzyme activity and phagocytosis of macrophage and production of ceruloplasmin were similar to those not treated with glucanase. These facts indicate that the induction of the activities of the former group requires longer contact of host cells with the glucan, and the latter group requires a shorter period to achieve fully active stages.

Acid Phosphatase↗

Physiochemical properties and antitumor activities of chemically modified derivatives of antitumor glucan "grifolan LE" from Grifola frondosa.

Antitumor glucan, grifolan LE (GRN LE), from Grifola frondosa was chemically modified to examine the structure-function relationship of the products. Modification by periodate, borohydride and acid hydrolysis of side chains of GRN LE did not alter properties such as helical conformation and antitumor activity of GRN LE. Introduction of carboxylic acid groups into the side chains by oxidation with periodate and with sodium chlorite (GRN LE-PC), and substitution with carboxymethyl (CM) or hydroxyethyl (HE) groups abolished the gel-forming ability of GRN LE. Significant antitumor activity was observed in all of the derivtives having gel-forming ability as well as some derivatives having no such ability. These results suggested that essential factors required for antitumor activity were (1----3)-beta-D-glucosyl linkages and high molecular weight, and that accessory groups could be linked to the main chain without loss of antitumor activity in a higher ratio than that of gel-forming ability.

Animals↗