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T Natori

Publications and source records attributed to T Natori.

At least 19 recordsLinked to original sources
PubMed2004

IL-12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll-like Receptor (TLR).

Agaricus blazei Murill is an edible fungus used in traditional medicine, which has various well-documented medicinal properties. In the present study, we investigated the effects of hemicellulase-derived mycelia extract (Agaricus blazei fraction H: ABH) on the immune system. First, we examined the cytokine-inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL-12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL-12 production by the CD14-positive cell population, consisting of monocytes/macrophages (Mo/Mphi). Furthermore, the elimination of Mo/Mphi attenuated IL-12 production in PBMC. ABH-induced IL-12 production was inhibited by anti-CD14 and anti-TLR4 antibodies but not by anti-TLR2 antibody. The activity of ABH was not inhibited by polymyxin B, while the activity of lipopolysaccharide used as a reference was inhibited. Oral administration of ABH enhanced natural killer (NK) activity in the spleen. These findings suggest that ABH activated Mo/Mphi in a manner dependent on CD14/TLR4 and NK activity.

Journal Article↗
PubMed2001

Glycolipid antigen processing for presentation by CD1d molecules.

The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(alpha1-->2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars to permit interaction with the T cell receptor. A lysosomal enzyme, alpha-galactosidase A, was responsible for the processing of Gal(alpha1-->2)GalCer to generate the antigenic monosaccharide epitope. These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids.

Amino Acid Motifs↗
PubMed1999

Examination of the pathogenesis of diabetic nephropathy in OLETF rats.

We conducted protein loading to examine the progression and pathogenesis of diabetic nephropathy. For this experiment, male OLETF, LETO, F344 and BN rats were used. This experiment was performed on rats between 5 and 30 weeks of age. Examination parameters included body weight, food intake, oral glucose tolerance test (OGTT), urinary protein level (UP), urinary albumin level (UA), glomerular filtration rate (GFR), kidney weights, light microscopy (LM) and electron microscopy (EM). In the protein-loaded OLETF group, the UP level was markedly increased 20 weeks or more after birth. In OLETF control group, GFR were higher than those in other strains. Glomerular hypertrophy and kidney weights were markedly increased in protein-loaded groups in OLETF rats. Thirty weeks after birth, EM showed that the number of polyethyleneimine (PEI) of the glomerular basement membrane (GBM) in protein-loaded OLETF group was significantly decreased compared to that in control group. These changes in OLETF rats were more marked in the protein-loaded group than those in the control group. LM showed that the number of exudative lesions with fibrin-cap in the protein-loaded OLETF group was significantly increased than those in control group. In OLETF rats, protein loading caused deterioration of nephropathy at 30 weeks of age. Therefore, it was demonstrated that not only blood sugar control but also protein intake factors play important roles in the deterioration of nephropathy in OLETF rats.

Albuminuria↗
PubMed1998

Effects of alpha- and beta-galactosylated C2-ceramides on the immune system.

In contrast to the immunosuppressive effects of C2-ceramide (C2-Cer), alpha-galactosylceramides with ceramides having more than 10 carbons in fatty acid chains have immunostimulatory activities. We therefore synthesized alpha- and beta-galactosylated C2-Cers in order to examine their effects on the immune system. beta-Galactosylated C2-Cer and C2-Cer suppressed the allogeneic mixed leukocyte reaction (MLR) responses, but alpha-galactosylated C2-Cer stimulated the MLR response.

Adjuvants, Immunologic↗
PubMed1998

Structure-activity relationship and conformational analysis of monoglycosylceramides on the syngeneic mixed leukocyte reaction.

We examined effects of alpha-, beta-galactosylceramides (CalCers) and alpha-, beta-glucosylceramides (GlcCers) on the syngeneic mixed leukocyte reaction (MLR) using spleen cells (responder cells) and dendritic cells (DC, stimulator cells). The DC pretreated with these alpha-monoglycosylceramides markedly stimulated the proliferation of spleen cells, in contrast to the little stimulatory effects produced by the DC pretreated with the corresponding beta-anomers. In addition, when we compared the effects of alpha-GalCer derivatives on the syngeneic MLR, it appeared that the 2"- and 3-hydroxyl groups in alpha-GalCers play a critical role in their stimulation of the MLR response. Based on these results, we performed a computer-aided molecular modeling study, and found that the orientations of the 2"-, 4"- and 3-hydroxyl groups common to alpha-GalCer and alpha-GlcCer are not accessible to those of inactive monoglycosyleeramides such as beta-GalCer. These results suggest that there might be a receptor-like site for alpha-monoglycosylceramides on the cells which are involved in the MLR response.

Animals↗
PubMed1997

RT1.P, rat class Ib genes related to mouse TL: evidence that CD1 molecules but not authentic TL antigens are expressed by rat thymus.

CD1 and TL were once thought to be genetic homologues because of their thymus-specific expression. We investigated their equivalents in the rat to clarify whether their structure and pattern of expression are conserved in rodents. Two rat class Ib genes, containing 3' sequences very similar to mouse TL, were identified and designated RT1.P. Neither of them, however, can encode ordinary class I molecules due to the accumulation of harmful mutations in the 5' regions that are unique to RT1.P, while the 3' TL-like regions still retain protein-coding capacity. Comparison of the structural organization of three types of TL family genes, which include mouse T3/T18-encoding TL antigens, mouse T1/T16, and rat RT1. P1/P2 pseudogenes, revealed the presence of a clear demarcation between the type-specific and TL-specific sequences at intron 3. This finding suggests that recombination plays an important role in creating the TL family genes in rodents. Characteristic features of TL, such as a low level of polymorphism and linkage to the major histocompatibility complex, were also observed in the rat. On the other hand, rat CD1 molecules were expressed at a high level on the surface of thymocytes. Absence of authentic TL antigens and thymic expression of CD1d molecules in the rat suggest the plasticity and conservation of class Ib genes in rodent evolution. Functions of TL may be substituted with CD1 or other class Ib molecules expressed by rat thymus.

Amino Acid Sequence↗
PubMed1997

Immunostimulatory activities of mono- or diglycosylated alpha-galactosylceramides.

We examined the effects of 2"- or 3"-monoglycosylated alpha-galactosylceramides (alpha-GalCers) and 2",3"-diglycosylated alpha-GalCers on allogeneic MLR and the proliferation of murine spleen cells. It was found that their ceramide portions greatly affect their immunostimulatory activities, and that the 3"-hydroxyl group plays a more important role in the immunostimulatory effects of alpha-GalCer derivatives than the 2"-hydroxyl group.

Adjuvants, Immunologic↗
PubMed1997

Immunostimulatory activities of monoglycosylated alpha-D-pyranosylceramides.

We compared the immunostimulatory effects of chemically synthesized alpha-galactosylceramides (alpha-GalCers), alpha-glucosylceramides (alpha-GluCers), 6"-monoglycosylated alpha-GalCer and 6"- or 4"-monoglycosylated alpha-GluCer and made the following observations: (1) the length of the fatty acid side chain in the ceramide portions greatly affects the immunostimulatory effects of alpha-GalCers and alpha-GluCers; (2) the configuration of the 4"-hydroxyl group of the inner pyranose moiety plays an important role in the immunostimulatory effects of monoglycosylated alpha-D-pyranosylceramides; (3) the free 4"-hydroxyl group of the inner pyranose of monoglycosylated alpha-D-pyranosylceramides plays a more important role in their immunostimulatory effects than the free 6"-hydroxyl group.

Adjuvants, Immunologic↗
PubMed1997

[Development of KRN7000, derived from agelasphin produced by Okinawan sponge].

New glycosphingolipids, named agelasphins, have been isolated as antitumoral compounds from an extract of a marine sponge, Agelas mauritianus. The absolute configurations of agelasphins were elucidated by the total synthesis. Various analogues of agelasphins were also synthesized and the relationship between their structures and biological activities was examined using an MLR assay. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application. KRN7000 markedly stimulated lymphocytic proliferation in allogeneic MLR, and showed potent tumor growth inhibitory activities in B16-bearing mice and strongly inhibited tumor metastasis, suggesting that KRN7000 is a potent biological response modifier. These biological effects were exerted by the activation of dendritic cells by KRN7000.

Animals↗
PubMed1996

A diabetogenic gene, ODB2, identified on chromosome 14 of the OLETF rat and its synergistic action with ODB1.

Genetic analysis of diabetogenic genes involved in developing spontaneous diabetes of NIDDM type in the OLETF rat was performed in (OLETF female X B N male)F2 and (OLETF female X BN male)F1 female X OLETF male backcross male offspring. In the F2 and/or backcross offspring, a high frequency of diabetes was found to be associated with a coat color gene, H (hooded). Since it is know that H gene is located on chromosome 14. an attempt was made to examine the linkage association of the gene responsible for elevating plasma glucose with various microsatellite markers of chromosome 14 in male F2 and/or backcross offspring. The results show that a high linkage exists with a microsatellite marker, D14Mit4 (LOD > 2). The gene was designated Odb2. It was also found that both genes, Odb1 which was previously found on chromosome X, and homozygous Odh2 are required to cause elevated plasma glucose in OGTT.

Animals↗
PubMed1996

Relationships between diet control and the development of spontaneous type II diabetes and diabetic nephropathy in OLETF rats.

The effect of a 30% restricted diet on the development of diabetes and diabetic nephropathy was examined using the Otsuka Long Evans Tokushima Fatty (OLETF) rat which develops non-insulin-dependent diabetes mellitus (NIDDM) spontaneously after 25-30 weeks of age. The first experimental group that received 30% restricted feeding from six to 80 weeks old, showed complete suppression of spontaneous diabetes up to 40 weeks of age and showed milder histopathological change of pancreatic islets, that those of the control group. The second group which received 30% restricted feeding during 30-80 weeks, showed a gradual decrease in clinical diabetes with age, even though they had already developed diabetes at 25 weeks. In both groups, levels of urinary protein content appeared to decrease, compared with that in control rats, although a gradual increase of urinary protein was observed with age. Histopathologically, glomerular damages were slight to mild in both groups. However, no improvement in nephrotic complication was observed for the group which received a 30% restricted feeding after 70 weeks of age. These results clearly show that the balanced-control diet, given at a 30% restricted feeding level and at an early phase, is effective in the prevention or improvement of NIDDM and nephrotic complications. Diet therapy after 70 weeks of age, however, had little or no effect.

Age Factors↗
PubMed1996

Enhancing effects of agelasphin-11 on natural killer cell activities of normal and tumor-bearing mice.

Agelasphin-11 (AGL-11), a novel alpha-galactosylceramide isolated from an extract of a marine sponge, Agelas mauritianus, markedly prolonged the life span of mice intraperitoneally inoculated with B16 cells. Since AGL-11 did not show any direct cytotoxic activity against B16 cells, this compound is considered to be a biological response modifier (BRM). We focused on the enhancing effect of this compound on in vivo natural killer (NK) cell activity because several BRMs have already been determined to enhance the in vivo natural killer (NK) cell activity. When we evaluated the enhancing activity of AGL-11 using normal mice, AGL-11 enhanced in vivo NK cell activity more potently than Poly I:C, which is a positive control. In addition, we examined the effect of this compound on the NK cell activity of tumor-bearing mice, and found that AGL-11 recovers the reduced NK cell activity in a tumor-bearing condition to a higher level than that of normal mice. These results suggest that AGL-11 shows antitumor activity by the activation of antitumor effector cells such as NK cells.

Animals↗
PubMed1995

Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice.

Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.

Animals↗
PubMed1995

A diabetogenic gene (ODB-1) assigned to the X-chromosome in OLETF rats.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat develops hyperglycemia, hyperinsulinemia and mild obesity, features that closely resemble those in human non-insulin-dependent diabetes mellitus (NIDDM). Here, we report a gene involved in the development of diabetes in OLETF rats. Segregation studies using OLETF and an unrelated strain, F344 showed that no diabetes was observed in F1 progeny and less than 12.5% of the F2 progeny developed diabetes, suggesting that multiple recessive genes are involved in the disease. Interestingly, diabetes was observed in approximately 40% of (OLETF female x LETO male) F1 male rats, whereas less than 4% of males were diabetic in the reverse F1 mating. This suggested that the LETO rat which has been established from the same original colony as the OLETF rat shares some, but not all, diabetogenic genes with the OLETF, and that one of the responsible genes locates on the X-chromosome. Linkage study using (OLETF female x F344 male)F2 progeny has confirmed that one of the diabetogenic loci in the OLETF rats locates on the X-chromosome 14 cM distant from the AR gene (LOD = 2.598) and has been designated as ODB-1.

Animals↗