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S Maruo

Publications and source records attributed to S Maruo.

At least 37 records · Page 2Linked to original sources

B cells regulate CD40 ligand-induced IL-12 production in antigen-presenting cells (APC) during T cell/APC interactions.

Although stimulation of freshly isolated murine spleen cells with anti-CD3 mAb or Con A failed to generate IL-12 production, the same cell preparations depleted of B cells produced IL-12. Addition of normal B cells inhibited IL-12 production in a cell number-dependent manner. IL-12 production was dependent on the presence of CD4+, but not of CD8+, T cells, and inhibited by addition of anti-CD40 ligand (CD40L) mAb. Anti-CD3 or Con A stimulation induced CD40L expression only on CD4+ T cells, which was inhibited in the presence of B cells. IL-12 production was also induced by interactions between CD40L-transfected Chinese hamster ovary cells and splenocytes depleted of T and B cells, but not of APC, indicating CD40L-induced IL-12 production by APC. The involvement of CD40 molecules was examined by comparing the ability of cells from CD40-deficient (CD40 -/-) and wild-type mice (CD40 +/+) to produce IL-12. Spleen cells from CD40 -/- and CD40 +/+ mice produced comparable amounts of IL-12 in response to bacterial stimuli. However, the B cell-depleted fraction from CD40 -/- mice failed to produce IL-12 when stimulated with anti-CD3 or Con A or when cocultured with CD40L-expressing Chinese hamster ovary cells. These results indicate that CD40L expressed on activated T cells induces APC to produce IL-12 through CD40/CD40L interaction, but this pathway is competitively inhibited by CD40+ B cells incapable of producing IL-12 upon stimulation with CD40L. Thus, this might represent a novel mechanism underlying the regulation of cell-mediated and humoral immunity.

Animals↗

Regulation of T cell-dependent and -independent IL-12 production by the three Th2-type cytokines IL-10, IL-6, and IL-4.

The production of IL-12 by macrophages/dendritic cells (Mphi/DC) is mediated either by a T cell-dependent pathway that is induced primarily by the interaction of CD40 ligand (CD40L) on activated T cells with CD40 on IL-12-producing cells or by a T cell-independent pathway that is induced by bacteria or bacterial products and enhanced by interferon-gamma (IFN-gamma). In this study we investigated the ability of the Th2-type cytokines interleukin (IL)-10, IL-6, and IL-4 to modulate IL-12 production in Mphi/DC induced through the two pathways. IL-12 production was induced in Mphi/DC from normal mice by stimulation with the combination of IFN-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan I (a model for the T cell-independent pathway) or by co-culture with Chinese hamster ovary (CHO) cells transfected with the CD40L (a model for the T cell-dependent pathway). The effects of three Th2-type cytokines on IL-12 production by Mphi/DC through the two pathways were examined. IL-10 inhibited IL-12 production induced through both pathways, although the inhibitory effect was more potent on the (IFN-gamma + LPS)-induced pathway. IL-6 inhibited only (LPS + IFN-gamma)-induced IL-12 production. The effect of IL-4 was particularly noteworthy: this cytokine inhibited (LPS + IFN-gamma)-induced IL-12 production, whereas it potentiated the production of IL-12 induced by CD40L. Regulation of IL-12 protein production by IL-10 and IL-4 was found to correspond to the levels of mRNA accumulation for the p40 and p35 IL-12 genes, whereas the presence of IL-6 during stimulation decreased IL-12 protein production without affecting steady-state mRNA levels. These results indicate that IL-12 production in Mphi/DC induced through a T cell-dependent or -independent pathway is positively or negatively regulated by particular cytokines at various control levels.

Animals↗

Establishment of an IL-12-responsive T cell clone: its characterization and utilization in the quantitation of IL-12 activity.

We previously demonstrated that proliferation of terminally differentiated Th1 clones depends primarily on an interleukin-12 (IL-12)-paracrine mechanism mediated by their interactions with antigen-presenting cells (APC) rather than on an IL-2-autocrine mechanism. Such a Th1 clone (4-86, C57BL/6 origin) was cultured with recombinant IL-12 (rIL-12) in the absence of either antigen or APC. Some cells survived for several passages of culture with only rIL-12, and by limiting dilution, several clones highly reactive to rIL-12 alone were obtained. One of these clones, designated 2D6, was found to proliferate strongly in response to less than 1 pg/mL of rIL-12. This clone exhibited the following surface phenotypes: CD3+, T cell receptor (TCR) alpha beta+, Vbeta11+, NK-1.1-; CD4-CD8-; LFA-1+, ICAM-1+; and CD28+, CD80+, CD86+, CTLA-4-. In accordance with high responsiveness to IL-12, 2D6 cells were also found to express IL-12 receptor (IL-12R) as detected by incubation with rIL-12 and then staining with anti-IL-12 monoclonal antibody (mAb). Stimulation of 2D6 with rIL-12 resulted in the expression of interferon-gamma (IFN-gamma) and IL-10 mRNAs and production of these cytokines. The 2D6 clone responded to IL-2 (vigorously), IL-7 (moderately), and IL-4 (mildly) in addition to IL-12. However, the Ab capture assay using anti-IL-12 mAb enabled us to quantify IL-12-specific activity contained in a given sample. Thus, this study describes the unique features of the IL-12-responsive T cell clone and demonstrates the utilization of this clone in the quantitation of a specific IL-12 activity.

Animals↗

Ceramic unicompartmental knee arthroplasty for spontaneous osteonecrosis of the knee joint.

Unicompartmental replacement with a ceramic knee prosthesis was performed in 10 patients with spontaneous osteonecrosis. The follow-up period averaged 42 months, with a range of 24 to 68 months. All of the knees received a Kyocera unicompartmental knee arthroplasty and all patients were evaluated using The Knee Society Clinical Rating System. The mean knee score increased from 50.6 to 90.8 at the last follow-up, showing no deterioration with time. All of the patients showed marked improvement of pain and excellent or good results were obtained in all cases. None of the patients had progressive radiolucency wider than 2 mm at the final follow-up. Ceramic unicompartmental knee arthroplasty is an acceptable treatment for spontaneous osteonecrosis of the knee joint; a satisfactory postoperative range of motion can be achieved, there are few complications, and a high initial success rate.

Aged↗

IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones.

We investigated the role of IL-12 in proliferation of various Th cell clones (class II-alloreactive (4-86 and 4-55) and keyhole limpet hemocyanin + self I-Ek-reactive (9-16)) following stimulation with Ag on APCs. These clones proliferated in response to stimulation with rIL-2, rIL-12, or Ag/APC. The proliferation induced by Ag/APC stimulation was not affected by anti-IL-2 Ab but was markedly inhibited by anti-IL-12 Abs. Consistent with this finding was the absence of detectable IL-2 activity in culture supernatants 12 to 48 h after Ag/APC stimulation, and the detection of significant levels of IL-12 in an Ab-capture bioassay. IL-12 was produced within 12 h after Ag/APC stimulation, reaching a peak after 18 to 24 h. The production of IL-12 in cultures of Th clones and APC contrasted with the production of IL-2 but not IL-12 upon allostimulation of primary T cells and the inhibition of their proliferation exclusively by anti-IL-2 Abs. Analysis of the expression of IL-12-binding sites on Th cells revealed low levels of IL-12 receptors in resting Th clones but high IL-12R levels 2 to 3 days after Ag/APC stimulation, declining gradually thereafter. The changes in IL-12R expression levels correlated closely with the IL-12 responsiveness of Th populations at various times after Ag/APC stimulation; Th populations obtained 3 and 10 days after Ag/APC stimulation exhibited very high and weak or marginal responsiveness to rIL-12, respectively, whereas the responses to rIL-2 were comparable in both Th populations. These results indicate that the Ag/APC-stimulated proliferation of terminally differentiated Th clones, in contrast to naive T cells, depends on the production of IL-12 by APC and on the simultaneous up-regulation of IL-12R on Th cells rather than on an IL-2 autocrine mechanism.

Animals↗

Spinal fractures resulting from the 1995 Great Hanshin Earthquake of the Kobe-Osaka area of Japan.

One of the worst earthquakes hit the Hanshin area between Kobe and Osaka, in the early morning at 5:46 AM on January 17th 1995. The destructive force with MG 7.2 severely damaged buildings, houses, roads and railways, leaving 6500 dead, and 34,900 injured. Hyogo College of Medicine located in this area was also severely damaged, thus there was a major challenge to provide post-quake medical support. A post-quake investigation in this area was done by 50 affiliated hospitals. More than 15,000 victim-patients were treated at these hospitals during the first 3 days after the quake. Major injuries were spinal fractures, and other trunk fractures, including rib or pelvis fractures, but fractures of long bones were uncommon, because the quake hit this area in the early morning when most people were asleep. In this study, the mechanisms of these major injuries were analysed by direct interview soon after the quake, with 230 victim-patients who had 140 spinal fractures, and 100 with rib or pelvis fractures. Most of those who had a spinal fracture had either sat up or stood up on their 'Futon' mattresses without bed frames and were struck on their backs by falling furniture or ceilings. On the other hand, patients who had fractures of the ribs or the pelvis had been lying in the supine or lateral position and were hit on their chest or pelvis. This characteristic lifestyle pattern of the Japanese people to lie down on the floor directly beside furniture, resulted in these injuries. From these results, we will emphasize the following precautions:- If an earthquake occurs during sleeping hours at home, do not stand up or sit up. The best position is to crouch on the 'Futon' mattress.

Adult↗

CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.

Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimulate the proliferation of B6 anti-bm12 CD4+ T cells. While stimulation in vitro to B6 splenic T cells with bm12 antigen-presenting cells (APC) induced IL-2 mRNA expression and IL-2 production, T cells stimulated with bm12 B cells expressed much less IL-2 mRNA and secreted very low but detectable levels of IL-2. Moreover, the T cells stimulated with the bm12 B cells did not proliferate and this was not corrected by the addition of rIL-2 responsiveness. Further, whereas IL-2 receptor (IL-2R) alpha chain expression was significantly induced on B6 T cells stimulated with bm12 APC; stimulation with bm12 B cells did not induce IL-2R expression over background levels. However, virgin T cells stimulated with both bm12 B cells and anti-CD28 mAb proliferated and displayed a dramatic increase in IL-2 production as well as IL-2R expression to levels commensurate with those resulting from bm12 B cells plus anti-CD28 mAb even in the presence of sufficient amounts of anti-IL-2 mAb for neutralizing produced IL-2; while levels of IL-2R were significantly lower compared to those induced in the absence of anti-IL-2 mAb, increased frequencies of IL-2R+ cells were comparable. Conversely, IL-2R was not induced by bm12 B cell stimulation in the presence of IL-2. Moreover, IL-2R expression and proliferation induced by stimulation with bm12 APC was inhibited by CTLA-4-Ig, a soluble recombinant fusion protein capable of blocking the CD28 co-stimulatory signals not only stimulate IL-2 production but also induce IL-2R expression by an IL-2-independent mechanism.

Abatacept↗

Enzymatic synthesis of 4-O-beta-D-galactopyranosyl-moranoline and 3-O-beta-D-galactopyranosyl-moranoline by using beta-galactosidase from Bacillus circulans.

A transgalactosylation reaction from lactose to moranoline (1-deoxynojirimycin) was accomplished by using beta-galactosidase [EC 3.2.1.23] from Bacillus circulans. The enzyme formed 3-O-beta-D-galactopyranosyl-moranoline and 4-O-beta-D-galactopyranosyl-moranoline as major products, together with 2-O-beta-D-galactopyranosyl-moranoline and 6-O-beta-D-galactopyranosyl-moranoline as minor ones.

1-Deoxynojirimycin↗

Utilization of intravenously infused maltooligosaccharides in rabbits.

The utilization of intravenously infused maltotriose, maltotetraose and maltopentaose was investigated in rabbits. Rabbits were infused with isotonic solutions of each maltooligosaccharide for 2 h and the utilization was assessed by the 24-h urinary loss of carbohydrates. The utilization of these maltooligosaccharides was good (> or = 87.5%) at a rate of 1 ml/kg/h (< or = 250 mg/kg/h) and poor (< or = 36.2%) at a rate of 5 ml/kg/h (> 250 mg/kg/h). Furthermore, these maltooligosaccharides infused as 5% solution showed good utilization (> or = 86.2%) at a rate of 5 ml/kg/h (250 mg/kg/h). These results suggest the existence of a threshold dose in the utilization of intravenously infused maltooligosaccharides, and this threshold value in rabbits is estimated to be nearly 250 mg/kg/h.

Animals↗

Effects of moranoline, 4-O-alpha-D-glucopyranosylmoranoline and their N-substituted derivatives on thermostability of cyclodextrin glycosyltransferase, glucoamylase, and beta-amylase.

In repeated glycosylmoranolines synthetic reaction at 55 degrees C, cyclodextrin glycosyltransferase (CGT-ase, EC 2.4.1.19) from Bacillus stearothermophilus retained its activity for more than 600 days. A main stabilizing compound was found to be 4-O-alpha-D-glucopyranosylmoranoline. The thermostabilizing activities of moranoline, 4-O-alpha-D-glucopyranosylmoranoline, and their N-substituted derivatives were studied. Moranoline and its N-substituted derivatives stabilized glucoamylase. 4-O-alpha-D-Glucopyranosylmoranoline and its N-substituted derivatives stabilized CGT-ase and beta-amylase.

1-Deoxynojirimycin↗

Clinical experience of ceramic cementless total knee arthroplasty in RA and a histological study of the bone-ceramic interface in revision cases.

The Kyoto total knee cementless prosthesis (KC-1) was used in 23 patients with rheumatoid arthritis. Its femoral component is made of alumina ceramics which articulated with a HDP plate supported by a ceramic plate. Although the followup period is short, the postoperative result is not satisfactory, because remarkable sinking of the tibial component was noticed in those patients who have bone atrophy. We had 6 cases of revision so far. Since 1986, we have been using bone cement in all cases of RA in doing TKA.

Adult↗

A novel and efficient method for enzymatic synthesis of high purity maltose using moranoline (1-deoxynojirimycin).

A transglycosylation reaction with moranoline (1-deoxynojirimycin) was done with soluble starch as the glucosyl donor and Bacillus macerans amylase as a cyclodextrin glycosyltransferase [EC 2.4.1.19]. The resultant transglycosylation products with moranoline, obtained by treating the reaction mixture with a strong cation exchange resin, were hydrolyzed by beta-amylase [EC 3.2.1.2] from sweet potatoes. The hydrolysate was treated with a strong cation exchange resin, and high purity maltose was obtained.

1-Deoxynojirimycin↗

A long-term follow-up study of unicompartmental replacement with a Marmor knee prosthesis and the introduction of a new ceramic prosthesis.

Unicompartmental replacement with a Marmor knee prosthesis was performed in 53 patients with unicompartmental osteoarthritis (OA). A five year or longer follow-up study of 15 joints in 13 of these patients was possible, three of which are now more than 10 years post-operative. All 13 patients reported absence of pain on weight-bearing and were able to flex the replaced knee more than 105 degrees. However, the postoperative femorotibial angle (FTA) appeared to be worsening with time, especially in those cases with an immediate postoperative FTA of more than 180 degrees. Since the needed size of the Marmor prosthesis is no longer available, we began using a ceramic prosthesis recently which we are introducing in this article.

Aged↗

Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. III. Analysis of regulatory cells suppressing the induction of thyroiditis.

It has previously been demonstrated that T cell clones with potentials to induce autoimmune thyroiditis exist in lymphoid organs from normal healthy individuals. The present study investigates the nature of regulatory cells co-existing in a normal lymphoid cell population to prevent the activation of these thyroiditis-inducing T cells. T cell-depleted (C57BL/6 x C3H/He) F1 mice (B cell mice) were prepared by adult thymectomy and injection of anti-thymocyte serum, followed by lethal X-irradiation and bone marrow reconstitution. Typical thyroiditis was induced in these B cell mice by i.v. administration of Lyt-1dull T cells but not of whole T cells from normal syngeneic mice. Additional injection of normal thymocytes into B cell mice which had been transferred with the Lyt-1 dull T cells resulted in complete prevention of thyroiditis induction. Mature thymocytes were responsible for this regulatory function and such regulatory cell activity was also found in peripheral lymphoid cells such as spleen cells. These regulatory cells exerted their capacity to prevent thyroiditis in cell dose-dependent and injection timing-dependent manners; thyroiditis was prevented when they were injected in cell doses of greater than 1.5 x 10(7)/mouse and before the initiation of the thyroiditis lesion. Most interestingly, the phenotypes of regulatory cells were Thy-1+ and L3T4+. Since the thyroiditis-inducing Lyt-1 dull T cells has previously been shown to be of L3T4+, these results indicate that there exist functionally heterogeneous subsets in an L3T4+ T cell population and that some L3T4+ T cells function as regulatory cells to prevent the activation of thyroiditis-inducing L3T4+ T cells co-existing in the normal lymphoid cell population.

Animals↗

T cell clones are killed by a thymic stromal cell monolayer following stimulation of T cell receptor with antigen and/or H-2 molecules on the monolayer.

A thymic stromal cell clone, MRL104.8a, expressed class I and class II H-2k antigens after exposure to gamma-interferon (gamma-IFN) and produced thymic stroma-derived T cell growth factor (TSTGF) irrespective of gamma-IFN exposure. Culturing the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted 9-16 helper T cell (Th) clone on an Ia (I-Ak and I-Ek)-expressing MRL 104.8a monolayer induced potent proliferation of the 9-16 cells by virtue of the TSTGF produced by the monolayer. In contrast, the addition of KLH to cultures resulted in lethal growth inhibition of the 9-16 Th clone. Such a phenomenon was also observed for various Th as well as cytotoxic T lymphocyte (CTL) clones, and the following were revealed: (i) the growth of the ovalbumin (OVA)-or bovine thyroglobulin (BTg)-specific Th clone on the la-expressing MRL 104.8a monolayer was also inhibited by addition of the relevant antigen. The fact that these Th clones required antigen-presenting cells (APC) capable of processing antigen for the recognition of the respective target antigen suggested the potential of MRL 104.8a cells for antigen-processing; (ii) the lethal growth inhibition of KLH-specific, I-Ak (23-1-8)- or I-Ek (9-16)-restricted Th clone was prevented selectively by anti-I-Ak or anti-I-Ek antibody respectively; (iii) the I-Ek-alloreactive Th clone (2-13) was supported for its growth on a gamma-IFN-unexposed MRL 104.8a monolayer, whereas this clone was killed on an I-Ek-expressing monolayer; and (iv) when I-Ak-reactive CTL clones were cultured on an Ia- or Ia+ monolayer, CTL clones failed to exhibit cytotoxic effect on either the Ia- or the Ia+ monolayer, but were conversely killed by the Ia+ monolayer. Its killing was also prevented by an antibody which inhibits the recognition of Ia antigen on the monolayer by CTL clones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗