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Biomedical subjects

R Teshima

Publications and source records attributed to R Teshima.

At least 37 records · Page 2Linked to original sources

Bone mass changes of tibial and vertebral bones in young and adult rats with collagen-induced arthritis.

To study the effect of arthritis on bone mass, bone mineral density (BMD) of cancellous and cortical bone in the tibial metaphysis and diaphysis in 2- and 7-month-old rats with collagen-induced arthritis (CIA) was serially measured using peripheral quantitative computed tomography (pQCT). BMD in the fourth lumbar vertebra in 7-month-old CIA rats was also measured by pQCT. The fourth lumbar vertebral body, distal femur, and proximal tibia in 7-month-old CIA rats were analyzed histomorphometrically. Changes in BMD differed between 2-month-old (young) and 7-month-old (adult) CIA rats. Although the BMD for the proximal tibia (2 mm and 5 mm distal from the growth cartilage) in young CIA rats decreased compared with that in control rats, the values exceeded the initial value during the arthritis course. On the other hand, bone loss in adult CIA rats occurred predominantly in the cancellous bone of the periarticular region of the tibia (2 mm distal from the growth cartilage), in which the enhancement of bone resorption and reduced bone formation were observed histomorphometrically. No remarkable changes were demonstrated in BMD or histomorphometrical analysis for the lumbar vertebra during the experimental course. These results suggest that bone loss in adult CIA rats resembles the osteoporosis that develops during the early stage of human rheumatoid arthritis. We conclude that adult CIA rats are more appropriate than young CIA rats as an experimental model of secondary osteoporosis due to rheumatoid arthritis.

Age Factors↗

Effects of ovariectomy and estrogen replacement therapy on arthritis and bone mineral density in rats with collagen-induced arthritis.

We investigated the effects of ovariectomy (ovx) and estrogen replacement therapy (ERT) on bone mineral density (BMD) and arthritis severity in rats with collagen-induced arthritis (CIA). Seven-month-old female Sprague-Dawley rats were separated into a sham group (n = 8), CIA group (n = 14), ovx group (n = 10), CIA + ovx group (n = 11), and CIA + ovx + ERT group (n = 14). In these groups, ovx was performed at 7 days, and ERT (17beta-estradiol at 20 microg/kg three times per week) was initiated 8 days after sensitization. Every 2 weeks, until 8 weeks after sensitization, arthritis score and hind paw thickness were evaluated, and BMD of the trabecular and cortical bones in the metaphysis and diaphysis of the tibia were measured by peripheral quantitative computed tomography. The arthritis score was highest in the CIA + ovx group at all timepoints after sensitization. The hind paw thickness was significantly higher in the CIA + ovx group than in the CIA group at 8 weeks after sensitization (p < 0.05). Both the arthritis score and hind paw thickness were lower in the CIA + ovx + ERT group than in the CIA + ovx group. BMD in the metaphysis was significantly decreased in both the trabecular and cortical bones in the CIA + ovx group compared with those in the CIA group at 4, 6, and 8 weeks after sensitization. In the CIA + ovx group, trabecular BMD was changed by -34 +/- 11%, and cortical BMD changed by -14 +/- 7% in the metaphysis at 8 weeks compared with those at 0 week. In the CIA group, changes of BMD in the metaphysis were -7 +/- 11% in trabecular bone and 0 +/- 7% in cortical bone. These differences of trabecular and cortical bone loss in the metaphysis were significant (both p < 0.01). BMD reduction was significantly less in the CIA + ovx + ERT group than in the CIA + ovx group at 6 and 8 weeks after sensitization. Although BMD in the diaphysis was also reduced in the groups with CIA, the degree of reduction was smaller than in the metaphysis. We conclude that ovx in CIA rats could enhance the severity of arthritis and bone loss, and that ERT could suppress arthritis and bone loss.

Animals↗

Regulation of mouse mast cell surface Fc epsilon RI expression by dexamethasone.

It is now clear that the mast cell's functional response to IgE-dependent stimulation can be influenced significantly by the level of expression of the high-affinity IgE receptor (Fc epsilon RI) on the cell's surface. Thus, modulation of Fc epsilon RI surface expression represents a potentially important mechanism for regulating mast cell activity in allergic reactions. In this study, we examined whether a glucocorticoid, dexamethasone (DEX), can influence levels of mast cell Fc epsilon RI expression either in the presence or absence of IgE, an up-regulator of the mast cell surface Fc epsilon RI level. In the absence of IgE, DEX decreased the surface Fc epsilon RI levels in mouse peritoneal mast cells, mouse bone marrow-derived cultured mast cells and a mouse mast cell line, Cl.MC/C57.1. Moreover, DEX also partially suppressed the ability of IgE to enhance surface expression of Fc epsilon RI in these cells. Three different glucocorticoids, DEX, methylprednisolone and hydrocortisone, suppressed Fc epsilon RI expression in mast cells, whereas sex steroids, i.e. estradiol, progesterone and testosterone, did not, indicating that the Fc epsilon RI-suppressing effect is glucocorticoid specific. On the other hand, DEX did not affect levels of Fc epsilon RI alpha, beta or gamma mRNA, suggesting that its ability to decrease surface Fc epsilon RI reflects a post-transcriptional mechanism. Finally, DEX-treated mast cells showed a reduced degranulation response to antigenic stimulation through down-regulation of surface Fc epsilon RI expression in addition to DEX-induced changes in downstream signals. These results show that mast cell surface Fc epsilon RI expression is suppressed by glucocorticoids in both the presence and absence of IgE, and suggest that reduction of mast cell surface Fc epsilon RI levels may be one of the favorable anti-allergic actions of glucocorticoids.

Animals↗

Tensile properties of rat anterior cruciate ligament in collagen induced arthritis.

OBJECTIVES: To investigate the effects of collagen induced arthritis (CIA) on the tensile properties of rat anterior cruciate ligament (ACL). METHODS: The tensile strength, bone mineral density (BMD), and histology of ACL units from rats with CIA were investigated. RESULTS: The tensile strength of the ACL unit was significantly lower in the rats with CIA at 10 weeks after immunisation (ultimate failure load, 74.9% of the control; stiffness, 62.0% of the control). The major mode of failure was femoral avulsion, and the BMD was significantly lower in the rats with CIA. A histological examination of the ligament insertion in rats with CIA showed resorption of the cortical bone beneath the ACL insertion and an enlarged mineralised fibrocartilage zone. CONCLUSIONS: These findings indicate that the decrease in tensile strength of ACL units correlated with histological changes in the ligament-bone attachment, such as bone resorption beneath the ligament insertion site and an enlargement of the mineralised fibrocartilage zone.

Analysis of Variance↗

Calcium signals in rat basophilic leukemia (RBL-2H3) cells primed with the neuropeptide substance P.

Communication between nerves and mast cells is a prototypic demonstration of neuroimmune interaction. We have recently shown that direct nerve-mast cell cross-talk can occur in the absence of an intermediary transducing cell and that the neuropeptide substance P is an important mediator of this communication. Here we study the calcium signals in rat basophilic leukemia cells (RBL-2H3; mucosal-type mast cells) primed with substance P. RBL cells responded only slightly to stimulation with compound 48/80, however they responded to the stimulation when the cells had been primed with substance P (0.5 microM) for one week. The present results provide a foundation to study the neuroimmune cross-talk in a co-culture system.

Animals↗

Bi-directional relationship of in vitro mast cell-nerve communication observed by confocal laser scanning microscopy.

Communication between nerves and mast cells is a prototypic demonstration of neuro-immune interaction. Recently, we used an in vitro co-culture approach comprising cultured murine superior cervical ganglia (SCG) and rat basophilic leukemia (RBL) cells to study this interaction. Previously, we concentrated mainly on the activation signal from neurites to mast cells (RBL). However, it is proposed that mast cell-nerve communication is not a one-sided relationship but a bi-directional one. In the present work, we studied the communication from mast cells to neurites. We observed that binding of anti-IgE receptor antibodies to mast cells increases calcium ion concentration [Ca2+]i in SCG neurites. This indicates that mast cell-nerve communication is bi-directional. Confocal fluorescence microscopic images indicated that [Ca2+]i in neurites increased after an increase of [Ca2+]i in mast cells. The lag-time of neurite activation was several times longer than that of mast cell activation. The correlation coefficient between the lag-times for mast cell and nerve activation was calculated to be 0.81. In addition, the fluorescence images showed that calcium signals in SCG neurites were able to extend to a long distance (100-200 microm) from the site where mast cells (RBL) attached to neurites.

Animals↗

[Hypersensitivity about environmental chemicals--mainly about food allergy].

The hypersensitivity of environmental chemicals and natural products has been reviewed. Among environmental chemicals, small molecular weight molecules work as hapten and cause immediate-type and delayed-type hypersensitivity. Among natural products, relatively lower molecular weight protein or glycoprotein (MW 10,000-70,000 kDa) work as allergen and cause mainly immediate-type hypersensitivity. In recent years, amino acid sequence of important natural allergens have been determined, and three-dimensional structure and IgE epitopes of some of these allergens have also been determined. The characteristics of both inhalation and food allergens have been summarized. As for food allergens, the stability of these proteins in simulated gastric fluid(SGF) was one of the most important characteristics. In the last parts, the approach to the assessment of allergenic potential of genetically modified foods has been summarized.

Allergens↗

[Expectations for alendronate in orthopedic surgery].

Alendronate is suggested not only to be useful for prevention of fracture as a treatment for osteoporosis but also to have an anti-inflammatory action. Moreover, as it is considered to be applicable for stress shielding, and prevention and treatment of osteolysis after arthroplasty, it is expected to be useful for the treatment of other orthopedic disorders as well as osteoporosis.

English Abstract↗

[Bone changes in osteoporosis associated with rheumatoid arthritis].

Low bone volume with reduced trabecular thickness and the increased eroded surface are common features in periarticular bone histology in patients with rheumatoid arthritis;however, there is no consensus on the change in bone formation. Main histological changes of iliac bone in rheumatoid arthritis are reduced bone volume, low trabecular thickness, and decreased trabecular connectivity caused by increased bone resorption. Results in parameters for bone formation are conflicting. The experimental model for arthritis demonstrates that bone turnover changes with the severity of arthritis.

English Abstract↗

Induction of active systemic anaphylaxis by oral sensitization with ovalbumin in mast-cell-deficient mice.

Mast-cell-deficient W/W(v) mice were sensitized by oral administration of 0.1 and 1.0 mg ovalbumin (OVA) by gavage every day for 9 weeks, and active systemic anaphylaxis (ASA) was induced by intraperitoneal injection of OVA. The production of OVA-specific IgE and IgG1 by oral immunization of the W/W(v) mice was high, and the production of IL-4 by splenocytes re-stimulated with OVA in vitro was increased. In contrast, production of OVA-specific IgG2a and IgG2b was low, and production of IFN-gamma by splenocytes after re-stimulation with OVA in vitro was rather decreased. These findings suggest that Th2-dominant helper T-cell activation had occurred. No increase in serum histamine level was observed following ASA induction. However, the plasma platelet-activating factor (PAF) levels of the mice sensitized with 0.1 and 1.0 mg OVA by gavage increased significantly. The increases in plasma PAF correlated well with the ASA-associated decreases in body temperature, suggesting that PAF plays an important role in ASA in W/W(v) mice. Taken together the above findings indicate that W/W(v) mice are a good model not only for studying induction of food allergy but also for examining the role of PAF in food-induced hypersensitivity.

Administration, Oral↗

A screening method for antigen-specific IgE using mast cells based on intracellular calcium signaling.

A simple screening method is presented for the measurement of antigen-specific IgEs in sera in which mast cells are used. This method is based on the intracellular calcium signal in mast cells induced by cross-linking the surface high-affinity Fc receptors (FcepsilonRIs) with IgEs and multivalent antigens. When a serum containing various antigen-specific IgEs is added to the mast cell suspension, various antigen-specific IgEs are captured by FcepsilonRIs on the cell surface. However, the required antigen-specific IgE can be specifically detected after the addition of the corresponding antigen. The resulting increase in intracellular calcium concentration ([Ca2+]i), monitored by Ca2+-fluorometry, was found to be an analytical measure for the screening of IgEs. Two kinds of rodent mast cells, cell-lined RBL2H3 cells and primary cultured BMMCs, were used as a representative model system of mast cells. A DNP hapten (DNP35-HSA) and ovalbumin (OVA) were chosen for illustrative antigens, and these antigen-specific IgEs (DNP-specific IgE, OVA-specific IgE) in the corresponding rodent sera were target antibodies. It was found that [Ca2+]i increased linearly with IgE concentrations ranging from 25 to 5000 ng/mL for DNP-specific IgE and from 5 to 50 ng/mL for OVA-specific IgE. For these dynamic ranges, optimum concentrations of antigens were found to be 10 ng/mL and 1 microg/mL for DNP35-HSA and OVA, respectively. It was concluded that by monitoring the increase of [Ca2+]i in mast cells, we could determine the antigen-specific IgEs. The present immunological assay based on the Ca2+ signal transduction in mast cells offers new possibilities for efficient screening of antigen-specific IgEs and the immunogenicity of IgE in sera.

Animals↗

Clinicoradiologic study of cervical laminoplasty with posterolateral fusion or bone graft.

STUDY DESIGN: A retrospective study of cervical expansive laminoplasty for cervical myelopathy from a clinicoradiologic perspective. OBJECTIVE: To clarify the correlation among sagittal curvature of the cervical spine, cervical range of motion, sagittal plane translation, spinal cord atrophy, and myelopathic symptoms in patients who have undergone laminoplasty. SUMMARY OF BACKGROUND DATA: Laminoplasties were developed to diminish the undesirable effects of laminectomy, which include postoperative kyphotic changes and instability. However, the superiority of laminoplasty over laminectomy remains controversial. METHODS: Fifty-one patients with cervical spondylotic myelopathy or ossification of the cervical posterior longitudinal ligament who underwent laminoplasty were radiologically assessed before and after surgery. The index of the sagittal curvature, intervertebral range of motion, listhesis, and the transverse area of the spinal cord at the site of maximal compression were measured to evaluate interrelations among those parameters and myelopathic symptoms. RESULTS: There were no patients with kyphotic curvature before surgery. The postoperative curvature tended to be less lordotic. This tendency did not adversely affect postoperative symptoms. The intervertebral range of motion was significantly decreased except at C1-C2. The final C4-C5 range of motion and the postoperative myelopathic symptoms were negatively correlated. A significant correlation was observed between the postoperative spinal cord atrophy and the final myelopathic symptoms. CONCLUSIONS: The decrease in the lordotic curvature index and the decrease in the intervertebral range of motion after laminoplasty did not cause neurologic deterioration. In the C4-C5 intervertebral segment with a high incidence of listhesis, the restriction of the C4-C5 range of motion improved the clinical myelopathic symptoms. The radiologic prognostic factors were the postoperative restriction of intervertebral range of motion in preoperatively unstable segments and the anatomic reversibility of spinal cord insult.

Aged↗

Identification of 142 single nucleotide polymorphisms in 41 candidate genes for rheumatoid arthritis in the Japanese population.

Single-nucleotide polymorphisms (SNPs) can make an important contribution to our understanding of genetic backgrounds that may influence medical conditions and ethnic diversity. We undertook a systematic survey of genomic DNA for SNPs located not only in coding sequences but also in non-coding regions (e.g., introns and 5' flanking regions) of selected genes. Using DNA samples from 48 Japanese patients with rheumatoid arthritis (RA) as templates, we surveyed 41 genes that represent candidates for RA, screening a total of 104 kb of DNA (30 kb of coding sequences and 74 kb of non-coding DNA). Within this 104 kb of genomic sequences we identified 163 polymorphisms (1 per 638 bases on average), of which 142 were single-nucleotide substitutions and the remainder, insertions or deletions. Of the coding SNPs, 52% were non-synonymous substitutions, and non-conservative amino acid changes were observed in a quarter of those. Sixty-nine polymorphisms showed high frequencies for minor alleles (more than 15%) and 20 revealed low frequencies (<5%). Our results indicated a greater average distance between SNPs than others have reported, but this disparity may reflect the type of genes surveyed and/or the relative ethnic homogeneity of our test population.

Alleles↗

Effect of Ca(2+) ATPase inhibitors on MCP-1 release from bone marrow-derived mast cells and the involvement of p38 MAP kinase activation.

The effect of two Ca(2+) ATPase inhibitors, cyclopiazonic acid (CPA) and 2,5-di-(tert-butyl)-1,4-hydroquinone (DTBHQ), on the release of MCP-1 from bone marrow-derived mast cells (BMMCs) were investigated. CPA and DTBHQ increased the intracellular free Ca(2+) concentration ([Ca(2+)](i)) and induced MCP-1 release in a dose-dependent manner. These Ca(2+) ATPase inhibitors induced MCP-1 release in the absence of phorbol ester, in contrast to their induction of TNF-alpha. MCP-1 release reached a maximum at 6-9 h. It was inhibited by treatment with actinomycin D, the immunosuppressant cyclosporin A, and the cytosolic Ca(2+) chelator BAPTA-AM. Furthermore, RT-PCR showed a time-dependent increase of MCP-1 mRNA. Thus MCP-1 release seems to depend on Ca(2+)-dependent transcriptional activation. MCP-1 release was dose-dependently inhibited by the p38 MAP kinase inhibitor SB202190, but not by the p44/42 MAP kinase inhibitor PD98059. Therefore, transcriptional activation of MCP-1 production and its release seem to be dependent on the nuclear factor of activated T cells and p38 MAP kinase activation. This is the first report to show the regulation of MCP-1 production in BMMCs.

Animals↗

Antiallergic effect of apple polyphenols on the allergic model mouse.

We studied here the antiallergic effect of apple condensed tannins (ACT) administered orally to a type I allergy model mouse transplanted with an IgEL a2 hybridoma secreting anti-2,4,6-trinitrophenyl (TNP) immunoglobulin E (IgE). The oral administration of ACT significantly inhibited the ear swelling responses at 1 h after antigen-stimulation with picryl chloride. The response was dose dependent within 0.1 to 10 mg/mouse. The inhibition of the ear swelling response reached the maximal level (90% inhibition) when ACT was administered 2 h before the antigen challenge. These findings suggest that ACT has an antiallergic effect on type I allergic symptoms.

Animals↗

Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P.

Communication between nerves and mast cells is a prototypic demonstration of neuroimmune interaction. However, whether mast cell activation occurs as a direct response to neuronal activation or requires an intermediary cell is unclear. Addressing this issue, we used an in vitro coculture approach comprising cultured murine superior cervical ganglia and rat leukemia basophilic cells (RBLs; possesses properties of mucosal-type mast cells). Following loading with the calcium fluorophore, Fluo-3, neurite-RBL units (separated by <50 nm) were examined by confocal laser scanning microscopy. Addition of bradykinin, or scorpion venom, dose-dependently elicited neurite activation (i.e., Ca2+ mobilization) and, after a lag period, RBL Ca2+ mobilization. Neither bradykinin nor scorpion venom had any direct effect on the RBLs in the absence of neurites. Addition of a neutralizing substance P Ab or a neurokinin (NK)-1 receptor antagonist, but not an NK-2 receptor antagonist, dose-dependently prevented the RBL activation that resulted as a consequence of neural activation by either bradykinin or scorpion venom. These data illustrate that nerve-mast cell cross-talk can occur in the absence of an intermediary transducing cell and that the neuropeptide substance P, operating via NK-1 receptors, is an important mediator of this communication. Our findings have implications for the neuroimmune signaling cascades that are likely to occur during airways inflammation, intestinal hypersensitivity, and other conditions in which mast cells feature.

Animals↗

Role of ecto-kinase in phorbol ester-enhanced growth hormone-binding protein release from human IM-9 cells.

Previously we reported that a phorbol ester, phorbol 12, 13-dibutyrate (PDBu), increased the release of human growth hormone-binding protein (hGH-BP) in IM-9 cells, and that this phorbol ester-enhanced release was mediated by protein kinase Ca (PKCalpha). In the present study, the mechanisms of the phorbol ester-enhanced hGH-BP release were further investigated. Treatment of IM-9 cells with PDBu did not increase hGH-BPs (55-60 kDa) in the intracellular soluble fraction. When the cells were treated with trypsin to remove human growth hormone receptors (hGHRs) on the cell surface after stimulation, no hGH-BPs were detected in the culture supernatants, nor did treatment with bafilomycin A1 or chloroquine affect the PDBu-enhanced hGH-BP release. These results suggest that hGH-BPs released by PDBu stimulation are derived from cell surface hGHRs and not generated within the cells. Protein kinase inhibitors with broad specificities, K-252a and K-252b, inhibited the PDBu-enhanced release with almost the same dose-dependency, although only a trace amount of K-252b was incorporated into IM-9 cells than K-252a, suggesting that K-252b probably inhibits an ecto-kinase extracellularly. PDBu actually enhanced the phosphorylation of several extracellular proteins, and this enhanced phosphorylation was completely inhibited by K-252b treatment. Moreover, the PKCalpha-specific inhibitor bisindolylmaleimide III which inhibits PDBu enhanced hGH-BP release inhibited the PDBu-enhanced phosphorylation of extracellular proteins. On the other hand, the impermeable PKC inhibitor PKC inhibitor peptide 19-31 did not inhibit PDBu-enhanced release, suggesting that the target PKCalpha for PDBu is not present on the extracellular surface. Taken together, these results suggest that, in addition to intracellular PKCalpha, activation of an undefined ecto-kinase may also be involved in the PDBu-enhanced hGH-BP release.

Carbazoles↗