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J Satoh

Publications and source records attributed to J Satoh.

At least 91 records · Page 5Linked to original sources
PubMed1995

Reduced expression of c-Fos in female NOD mouse thymocytes and up-regulation with human lymphotoxin.

Previously we reported that the administration of human (h) lymphotoxin (h-LT) markedly protected NOD mice from insulin-dependent diabetes mellitus (IDDM) partly by affecting the generation phase of anti-islet effector cells, probably in the thymus. In this study, we investigated the effect of h-LT on the signal transduction of the mouse thymocytes by observing c-Fos expression in the thymocytes by using a flow cytometer. The intensity of c-Fos expression in whole thymocytes was significantly lower in the female NOD with a high incidence of diabetes than that in the male NOD mice with a low incidence of diabetes and than that in normal mice (P < 0.0001). The low c-Fos expression in the female NOD thymocytes was most prominent in CD3low thymocytes. c-Jun expression of the CD3low thymocytes was also lower in the female NOD mice. Administrations of h-LT, h-TNF, and h-IL-2, which has been reported to prevent IDDM in NOD mice by systemic administration, significantly up-regulated c-Fos expression in CD3low thymocytes. From these results, it is assumed that a relationship may exist between the high diabetes incidence and the defective c-Fos expression in female NOD mice and between the prevention of IDDM and the amelioration of the defective c-Fos expression with h-LT in female NOD mice.

Animals↗
PubMed1995

Analysis of action mechanism of lymphotoxin in prevention of cyclophosphamide-induced diabetes in NOD mice.

Recently we reported that lymphotoxin (LT) administration protected non-obese diabetic (NOD) mice and BB rats from insulin-dependent diabetes mellitus. In this study we analysed the protection mechanism of LT by using cyclophosphamide (CY)-induced autoimmune diabetes in NOD mice. Pre-administration of 500 or 1000 U of LT three times a week between the age of 4 and 11-13 weeks before CY-treatment strongly inhibited CY-induced diabetes. This inhibition was reproduced by LT pre-administration at an earlier age (4 to 7 weeks) but not at a later age (8 to 11 or 10 to 12 wks). LT post-administration (100 U daily or 500 U twice a week) after CY-treatment at 14 weeks of age also strongly inhibited CY-induced diabetes. Spleen cell transfer was carried out using various combinations of donors and recipients. Spleen cell transfer from the non-diabetic mice, which were LT pre-administered between the age of 4 and 13 wks, to CY-treated mice did not significantly inhibit CY-induced diabetes, while transfer of the cells from the similarly treated mice to irradiated recipients did induce diabetes although the onset of diabetes was significantly delayed. Diabetes was not transferred by spleen cells from diabetic mice to LT pre-administered and CY-treated mice. LT administration did not change subpopulations and adhesion molecule expressions of the spleen lymphocyte. Taken together, these results suggest that LT protects NOD mice from CY-induced diabetes by making the mice resistant to autoimmune diabetes and possibly by suppressing anti-islet effector cells, but not by inducing adoptively transferable suppressor cells, although the precise mechanisms still remain to be elucidated.

Animals↗
PubMed1995

Cytokines and growth factors induce HSP27 phosphorylation in human astrocytes.

In previous studies, an enhanced expression with abnormal phosphorylation of a low molecular weight heat shock protein, HSP27, was identified in reactive astrocytes and Rosenthal fibers in Alexander disease brain. To investigate the relevance of HSP27 to the pathological change of astrocytes, phosphorylation of HSP27 was examined in astrocyte cultures isolated from fetal human brains. In unstimulated human astrocytes, HSP27 was identified in the cytoplasm and was comprised of a major unphosphorylated "a" isoform and a minor monophosphorylated "b" isoform. The level of HSP27 phosphorylation was elevated greatly after a 30 minute exposure to heat shock, sodium arsenite, interleukin-1 (IL-1 alpha and IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) with an increased expression of a diphosphorylated "c" isoform. Treatment with interferon-beta (IFN-beta), platelet-derived growth factor-AA, leukemia inhibitory factor, phorbol 12-myristate 13-acetate, and dibutyryl cyclic AMP stimulated phosphorylation of HSP27 moderately, while IFN-gamma, TNF-beta, basic fibroblast growth factor, epidermal growth factor, or fetal bovine serum did not significantly alter the level of HSP27 phosphorylation. Total amount of the HSP27 protein and its cytoplasmic localization were unaffected by any of these reagents. These results indicate that HSP27 is a constitutive protein in human astrocytes. The induction of HSP27 phosphorylation by a specific set of cytokines and growth factors suggests that HSP27 is a key cellular substrate by which signaling events are mediated in human astrocytes under normal and pathological conditions.

Astrocytes↗
PubMed1995

Prostate-specific antigen in mass screening for carcinoma of the prostate.

BACKGROUND: Prostate-specific antigen (PSA) has various advantages over prostatic acid phosphatase (PAP) as a marker for prostate cancer, but its role in prostate cancer mass screening remains controversial. We measured serum PSA in addition to serum PAP determination and digital rectal examination (DRE) in our mass screening program to assess the usefulness of PSA for prostate cancer mass screening. METHODS: Serum PSA and PAP measurements and DRE were performed in 1249 patients in mass screening for carcinoma of the prostate in 1989 and 1990. Thirteen cancers were diagnosed. We calculated the mean plus standard deviations (2SD) of the PSA and PAP values of men without cancer, and assessed the usefulness of PSA for prostate cancer screening by using these figures as the upper limit of normal. RESULTS: The number positive for PSA, PAP and DRE were 39, 36 and 48, respectively. If our screening had been performed without DRE, three cancers would have remained undetected, and the number would have been the same if performed without PSA. If the screening had been performed without PAP, on the other hand, no cancers would have remained undetected. The sensitivities of PSA and PAP were 54% and 23%, respectively. The screening detection rate with DRE and PSA was 0.88%, and with DRE and PAP was 0.64%. CONCLUSIONS: Measurement of serum PSA values with adjustment of the cut-off value was considered more useful than PAP in mass screening for prostate cancer.

Acid Phosphatase↗
PubMed1995

Ganglioside markers GD3, GD2, and A2B5 in fetal human neurons and glial cells in culture.

Expression of ganglioside markers GD3, GD2, and A2B5 was investigated in primary cell cultures isolated from fetal human brains of 12-15 weeks' gestation by immunocytochemistry. None of neuron-specific enolase (NSE)+ neurons expressed GD3, while large numbers of NSE+ neurons expressed GD2 (72%) or A2B5 (48%). In GFAP+ astrocytes, GD3 was expressed in a small population (3%) with a high proliferative capacity. GD2 expression was observed in 20% of GFAP+ astrocytes, while A2B5 was identified in a very small number (2%) of GFAP+ astrocytes. GD2 was coexpressed in a small population (11%) of GD3+ astrocytes, while A2B5 was colocalized in more than 50% of GD3+ astrocytes. In galactocerebroside+ oligodendrocytes, GD3 expression was not observed but a small population (8-9%) expressed GD2 and A2B5. In Ricinus communis agglutinin (RCA)+ microglia, neither GD3, GD2, nor A2B5 were identified. Our results indicate that in fetal human brain cell cultures, GD3 is expressed in a small population of astrocytes, while both GD2 and A2B5 are expressed in a large population of neurons and smaller populations of astrocytes and oligodendrocytes. Our results suggest that both GD3 and A2B5, cell type-specific markers for oligodendrocyte-type 2 astrocyte progenitor cells in the rat central nervous system, could not be utilized as valid markers for glial precursor cells in fetal human brain cell cultures.

Bromodeoxyuridine↗
PubMed1995

Estramustine phosphate for preventing flare-up in luteinizing hormone-releasing hormone analogue depot therapy.

The usefulness of estramustine phosphate (ECT) for preventing flare-up in goserelin acetate depot therapy for advanced prostate cancer was studied. Pretreatment with ECT 560 mg daily for 3 weeks almost completely prevented the rise in testosterone level seen in goserelin acetate depot therapy and no signs or symptoms of tumor flare were observed. Long-term ECT completely blocked the rise in luteinizing hormone and testosterone level, but ECT at this dosage was likely to cause complications. The administration of ECT 560 mg daily for 3 weeks prior to goserelin acetate depot therapy was considered sufficient to prevent tumor flare, and its effect was considered to be more marked than that of short-term treatment with antiandrogens.

Acid Phosphatase↗
PubMed1995

Differential effects of beta and gamma interferons on expression of major histocompatibility complex antigens and intercellular adhesion molecule-1 in cultured fetal human astrocytes.

We investigated the modulatory effects of human interferon beta (IFN-beta) and gamma (IFN-gamma) on expression of class I and II major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1) in fetal human astrocytes in culture using flow cytometry and immunocytochemistry. Under the baseline condition, class I MHC antigen and ICAM-1 were expressed in a moderate number (23 to 76%) of astrocytes, whereas class II MHC antigen was expressed in only a small number (0.3 to 8%) of astrocytes. Following a 72-hour treatment with IFN-gamma (10 to 100 U/ml), expression of all three antigens increased greatly. Expression of class I MHC antigen was also elevated by exposure to IFN-beta (10 and 100 IU/ml). However, IFN-beta did not significantly induce expression of class II MHC antigen or ICAM-1. Furthermore, IFN-beta significantly reduced IFN-gamma-induced expression of class II MHC antigen but not of class I MHC antigen or of ICAM-1. The differential effects of IFN-beta and IFN-gamma on expression of class I and II MHC antigens and ICAM-1 in fetal human astrocytes suggest that interferons serve as modulators of astrocyte function at sites of inflammation in the human CNS.

Abortion, Legal↗
PubMed1995

Light and electron microscopic localization of lipids in Blastocystis hominis.

Localization of the lipid of Blastocystis hominis was histochemically demonstrated. B. hominis was fixed with glutaraldehyde, treated with detergents, and stained with Sudan black B or Nile blue. The central vacuole of B. hominis stained with Sudan black B showed many black droplets with great variation in staining intensity. In Nile blue staining, the central vacuole showed many pinkish granules or homogeneous blue reactions. These results indicated the presence of neutral lipids and/or acidic lipids in the central vacuole. At the ultrastructural level, the central vacuole and some cytoplasmic vesicles showed enhanced electron density after post-fixation with imidazole-buffered osmium tetroxide solution. Great variation in the density and distribution of the electron-dense materials was observed in the central vacuole. Since the electron-dense vesicles were frequently observed in the cytoplasm, B. hominis may accumulate the lipid in the central vacuole, the function of which is not well known.

Animals↗
PubMed1995

[Essential thrombocythemia transformed to minimally differentiated acute myeloid leukemia].

A 64-year-old female diagnosed for essential thrombocythemia was treated with MCNU 50 mg four times in the course of the disease. Six months after the last administration, in May 1991, she was admitted because of decreasing thrombocyte count and appearance of blasts in the peripheral blood. On admission, laboratory findings were as follows: WBC 700/microliters with 5% of blasts, RBC 331 x 10(4)/microliters, and PLT 17.9 x 10(4)/microliters. Bone marrow aspiration revealed hypocellular marrow with 39% blasts. About 5% of the blasts were positive for myeloperoxidase by electron microscopy analysis. Leukemic cells were positive for CD 7, 13, 33 and 34, negative for other lymphoid lineage markers, and demonstrated no rearrangement of TCR-beta, gamma and IgH genes. Although she was treated with low-dose cytosine arabinoside, no response was observed. Subdural hematoma and sequential pneumonia developed and the patient died eight months after leukemic transformation. In conclusion, we think that the leukemic transformation might have been developed in the natural course of essential thrombocythemia in the present case. However, we cannot exclude the influence of MCNU.

Cell Transformation, Neoplastic↗
PubMed1994

Proliferation and differentiation of fetal human oligodendrocytes in culture.

Phenotypic expression and proliferative capacity of the cells of oligodendrocyte lineage were investigated in primary cultures isolated from fetal human brains of 12-15 weeks' gestation using double immunolabeling with Ranscht-monoclonal antibody (R-mAb) or O4 and antibromodeoxyuridine (BrdU) antibody. Cultured cells of oligodendrocyte lineage consisted of a major population of R-mAb+O4- cells and minor populations of R-mAb-O4+ and R-mAb+O4+ cells. Most of the R-mAb+O4- cells exhibited a uni-, bi-, or tripolar immature morphology, while the majority of the R-mAb+O4+ cells exhibited a multipolar mature morphology. R-mAb-O4+ cells contained a mixture of immature and mature cell types. When incubated in serum-free culture medium containing BrdU for 4 days, 42% of total oligodendrocytes expressed nuclear BrdU immunolabeling. R-mAb+ cells exhibited a higher degree of BrdU immunolabeling, indicating that they have greater capacities for proliferation than O4+ cells. The large majority of BrdU+ cells exhibited an immature morphology. Inclusion of insulin, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), or fetal bovine serum in culture medium did not stimulate proliferation of oligodendrocytes, while platelet-derived growth factor (PDGF) or PDGF plus bFGF increased the number of R-mAb+BrdU+ and O4+BrdU+ cells over control, even though the results were not statistically significant. In addition, insulin and IGF-I induced a 3-fold increase in the number of R-mAb+O4+ cells, indicating that they promoted differentiation of oligodendrocytes. The present study indicates that fetal human oligodendrocytes in culture exhibit a considerable degree of proliferative capacity without requirement of exogenous growth factors and that both insulin and IGF-I promote their differentiation.

Animals↗
PubMed1994

HSP72 induction by heat stress in human neurons and glial cells in culture.

Expression of 72-kDa heat shock protein (HSP72) induced by heat stress was investigated in cultured neurons and glial cells isolated from fetal human brains using immunoblotting and immunocytochemistry. Under the unstressed condition, a low level of HSP72 expression was observed in astrocytes, microglia, oligodendrocytes, and neurons. Under the heat-stressed condition, an increased expression of HSP72 was observed in all cell types with specific location in the nuclear and cytoplasmic regions. Following heat stress, HSP72 was expressed intensely in more than 50% of astrocytes and microglia during 8-24 h post-recovery, while it was detectable in only 9% of oligodendrocytes and 3% of neurons at 48 h post-recovery. These results indicate that heat stress induces a predominant expression of HSP72 in astrocytes and microglia, and more limited HSP72 expression in oligodendrocytes and neurons in fetal human neural cells in culture. The differential patterns of HSP72 induction in human neural cells by heat stress suggest that cellular mechanisms by which the heat shock response is regulated are different among various cell types in the human central nervous system.

Astrocytes↗
PubMed1994

Differential expression of Lewis(x) and sialyl-Lewis(x) antigens in fetal human neural cells in culture.

Lewis(x) is a cell-surface carbohydrate antigen defined by the trisaccharide structure, Gal beta 1-->4 (Fuc alpha 1-->3) GlcNAc. Expression of Lewis(x) and sialyl-Lewis(x) antigens in primary cell cultures isolated from fetal human brains of 12-15 weeks gestation was investigated by double immunolabelling with antibodies against monomeric Lewis(x) (4C9), oligomeric Lewis(x) (FH4), and sialylated oligomeric Lewis(x) (FH6) antigens and cell type-specific markers. The monomeric Lewis(x) antigen was expressed in more than 15% of astrocytes and 100% of oligodendrocytes, whereas it was not identified in neurons or in microglia. The oligomeric Lewis(x) antigen was undetectable in any cell types, while the sialylated oligomeric Lewis(x) antigen was expressed in more than 95% of microglia but not in any other cell types. The cell type-specific expression of Lewis(x) and sialyl-Lewis(x) antigens in fetal human glial cells suggests that these fucose-containing carbohydrate molecules play roles in intercellular recognition between distinct cell types during the development of the human central nervous system.

Antibodies, Monoclonal↗
PubMed1994

HSP72 induction by heat stress is not universal in mammalian neural cell lines.

Heat-induced expression of 72-kDa heat shock protein (HSP72) was investigated in a panel of neuronal and non-neuronal cell lines by immunoblotting and immunocytochemistry using monoclonal antibodies directed to HSP72. By immunoblotting, HSP72 expression was observed in most cell lines of mouse (SN6.1b, CL8c4.7, NSC34.6, B2A, C2C12), rat (PC12, C-6, L3), and human (NB-1, GOTO, IMR-32, HeLa) origin under the heat-stressed condition. The mouse neuroblastoma cell line N18TG2, however, did not express HSP72 under the heat-stressed condition. By immunocytochemistry, HSP72 was undetectable in the heat-stressed N18TG2 cells, while it was identified in the heat-stressed SN6.1b cells, a clonal hybrid neuron between N18TG2 and mouse septal cholinergic neuron. By exposure to a priming sublethal heat shock, SN6.1b cells but not N18TG2 cells acquired a significant level of tolerance to a subsequent lethal heat shock. These results suggest that heat-induced expression of HSP72 may contribute to acquisition of the thermotolerant state in SN6.1b cells.

Animals↗
PubMed1994

Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats.

We previously reported that the in vivo production of the tumor necrosis factor alpha (TNF) was significantly enhanced after the onset of diabetes in spontaneous type 1 and 2 diabetic animals. In this report we confirmed the enhanced production of TNF in streptozotocin (STZ)-induced diabetes and then attempted to suppress the enhanced TNF production with N-acetylcysteine (NAC), a precursor of glutathione synthesis. The lipopolysaccharide-induced serum TNF activities were significantly enhanced in STZ-induced diabetic rats (6-18 weeks of age) compared with those of nondiabetic rats throughout the 12-week experiment. A single, oral administration of NAC (200 or 1000 mg/kg body wt) significantly suppressed the enhanced TNF production in the diabetic rats compared with that in untreated rats in a dose-dependent manner. On the other hand, in the long-term (6 or 12 weeks) administrations, smaller doses of NAC (50 or 200 mg/kg/day) also significantly inhibited the enhanced production of TNF regardless of the dose of NAC. NAC administration, however, did not suppress the TNF production of nondiabetic rats. The long-term NAC administration affected neither body weight nor levels of serum glucose, fructosamine, albumin, and triglyceride. These results show that NAC administration significantly suppressed the enhanced TNF production in diabetic rats and indicate that NAC might be useful in preventing TNF-mediated pathological conditions in diabetes.

Acetylcysteine↗
PubMed1994

A novel complex mutation in the LDL receptor gene probably caused by the simultaneous occurrence of deletion and insertion in the same region.

A novel complex mutation with the presence of both deletion and insertion in very close proximity in the same region was detected in exon 8 of the LDL receptor gene from two apparently unrelated Japanese families with familial hypercholesterolemia (FH). In this mutant LDL receptor gene, the nine bases from nucleotide (nt) 1115 to nt 1123 (AGGGTGGCT) were replaced by six different bases (CACTGA), and consequently the four amino acids from codon 351 to 354, Glu-Gly-Gly-Tyr, were replaced by three amino acids, Ala-Leu-Asn, in the conserved amino acid region of the growth factor repeat B of the LDL receptor. The nature of the amino acid substitution and data on the families suggest that this mutation is very likely to affect the LDL receptor function and cause FH. The generation of this complex mutation can be explained by the simultaneous occurrence of deletion and insertion through the formation of a hairpin-loop structure mediated by inverted repeat sequences. This this mutation supports the hypothesis that inverted repeat sequences influence the stability of a given gene and promote human gene mutations.

Amino Acid Sequence↗
PubMed1994

Rapidly proliferating glial cells isolated from adult mouse brain have a differentiative capacity in response to cyclic AMP.

A glial cell line designated as B2 was generated from primary cultures of oligodendrocytes/astrocytes isolated from an adult BALB/c mouse brain and maintained for over 1 year. Phenotypic characteristics of B2 cells were investigated by immunolabeling with cell type-specific markers for oligodendrocytes (O4 and galactocerebroside (GalC)), astrocytes (glial fibrillary acidic protein (GFAP)), and immature neuroectodermal cells (vimentin). When cultured in a serum-containing medium, B2 cells exhibited a bipolar or a tripolar process-bearing morphology and proliferated with a 24-28 h doubling time, without requirement of exogenous growth factors. Under this culture condition, vimentin was identified in all of the B2 cells, GFAP in 7%, and O4 and GalC in less than 1% of the cells. When cultured in a serum-free medium containing 1 mM dibutyryl cyclic AMP (dbcAMP), B2 cells extended longer processes and 45% of the cells expressed cell type-specific markers for oligodendrocytes or astrocytes. GFAP was identified in 29% of B2 cells, O4 in 16%, and GalC in 6% of the cells, although, neither O4+GFAP+ nor GalC+GFAP+ cells were observed. B2 cells proliferated in response to phorbol 12-myristate 13-acetate (PMA), basic fibroblast growth factor (bFGF), insulin, insulin-like growth factor (IGF-I) and platelet-derived growth factor (PDGF), but not to dbcAMP, forskolin (FK), or retinoic acid (RA). These results indicate that B2 cells are distinct from typical oligodendrocytes and astrocytes with respect to their great proliferative potential, and suggest that B2 cells, with a capacity to differentiate into oligodendrocytes and astrocytes in response to cyclic AMP, may represent a population of glial precursor cells in the adult mouse central nervous system (CNS).

Animals↗