PubMed Health⌕ Search

Biomedical subjects

K Nishijima

Publications and source records attributed to K Nishijima.

At least 55 records · Page 3Linked to original sources

Study on the superoxide-producing enzyme of eosinophils and neutrophils--comparison of the NADPH oxidase components.

It has been known that eosinophils produce more superoxide anion (O2-) than neutrophils. To elucidate the mechanism involved in the difference in the superoxide-producing activities, we compared the NADPH oxidase components and the translocation of the cytosolic components between eosinophils and neutrophils. Membrane-bound cytochrome b558, cytosolic p47-phox, p67-phox, and p40-phox were present in both neutrophils and eosinophils, but the amounts of these components were 1.5- to 3.3-fold greater in eosinophils than neutrophils. Upon activation, p47-phox, p67-phox, and p40-phox were translocated to the membranes in both leukocytes, but larger amounts were translocated in eosinophils than in neutrophils. Furthermore, the cross-mixing experiments using membrane and cytosol of eosinophils and neutrophils revealed that more cytosolic components were translocated, and more superoxide-producing activities were obtained using eosinophil fractions. Interestingly, Km values of activated oxidase for NADPH were almost the same in any combination of membrane and cytosol from both leukocytes, indicating that oxidase components are likely similar in both eosinophils and neutrophils. These observations suggest that NADPH oxidase components are more abundant in eosinophils than neutrophils, and, upon activation, larger amounts of NADPH oxidase complex are formed in eosinophils than in neutrophils.

Amino Acid Sequence↗

Metaphyseal fibrous defect (nonossifying fibroma) in the mandible. A case report.

A 7-year-old boy presented in whom a metaphyseal fibrous defect was diagnosed. The lesion was enucleated under local anesthesia. The postoperative course was uneventful and there have been no signs of recurrence as of 14 months after operation. Although rare, metaphyseal fibrous defect should be included in the differential diagnosis of tumors arising in the jaws.

Bone Diseases, Developmental↗

Enhancing effect of interleukin-4 on the secretion of interferon-gamma by alpha s1-casein-specific CD8+ T cells.

alpha s1-Casein-specific CD8+ T cell clones expressed the interleukin (IL)-4 receptor, although they did not secrete detectable IL-4. We found that IL-4 significantly enhanced the secretion of interferon (IFN)-gamma by these CD8+ T cell clones. IL-4 also enhanced the secretion of IFN-gamma induced by stimulating the immobilized anti-CD3 antibodies of polyclonal CD8+ T cells which had been isolated from lymph nodes and were stimulated in vitro with the immobilized anti-CD3 antibody and IL-2. In addition, IL-4 added at the time of this first in vitro stimulation induced strong IFN-gamma productivity, as well as IL-4 and IL-10 productivity, which were detectable upon restimulation of these cells. Results are discussed in relation to the inhibitory effects of IFN-gamma production on IL-4-producing cells.

Animals↗

Differential effects of phencyclidine and methamphetamine on dopamine metabolism in rat frontal cortex and striatum as revealed by in vivo dialysis.

We have examined the effects of schizophrenomimetic drugs including phencyclidine (PCP) and methamphetamine (MAP) on cortical and striatal dopamine (DA) metabolism using an in vivo dialysis technique in the rat. An acute systemic injection of PCP (2.5-10 mg/kg, intraperitoneally (i.p.)) dramatically increased concentrations of DA, 3,4-dihydroxy-phenylacetic acid, and homovanillic acid in the dialysates from the medial frontal cortex in a dose-dependent fashion. However, PCP (2.5-10 mg/kg, i.p.) caused a much lower augmentation of extracellular DA release, with a significant decrease in dialysate DOPAC levels in the striatum. Moreover, continuous infusion of tetrodotoxin (TTX, 10(-5) M) into the prefrontal or striatal region through the microdialysis tube completely blocked the ability of PCP (10 mg/kg, i.p.) to alter the extracellular release of DA and its metabolites in the respective areas. In contrast, MAP (4.8 mg/kg, i.p.) elicited a marked and tetrodotoxin-resistant increase in DA levels with a significant loss of DOPAC contents in the extracellular space of both the frontal cortex and the striatum. The present results clearly demonstrate the differential effects of PCP on cortical and striatal DA transmission, suggesting that PCP may facilitate DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area, whereas PCP-induced elevation of extracellular DA in the striatum may be caused mainly by reuptake inhibition of DA liberated by basal activity of the striatal DA neurons. The regional variation in PCP-induced DA release would be due to the combination of NMDA (N-methyl-D-aspartate) receptor blocking and DA reuptake inhibition by the drug. The uniform and TTX-resistant nature of MAP-induced changes in brain DA metabolism may result from the direct actions of MAP at DA nerve terminals.

3,4-Dihydroxyphenylacetic Acid↗

[Heparin affinity high-performance liquid chromatography as an alternative to bioassay of CS23 mutein of recombinant human basic fibroblast growth factor].

We investigated whether a chemical assay by high-performance liquid chromatography (HPLC) as an alternative to the complicated and time-consuming bioassay for CS23 mutein of recombinant human basic fibroblast growth factor (rhbFGF-CS23) using the fetal bovine heart endothelial cell line ATCC CRL 1395. Physically, chemically or enzymatically denatured rhbFGF-CS23 was subjected to heparin affinity (HA)-HPLC and the bioassay. Good agreement was observed between the results obtained by these two methods. Moreover, HA-HPLC gave much more reproducible results (RSD = 1.9%, n = 6) than the bioassay (RSD = 7.4%, n = 18). HA-HPLC is therefore a simple, accurate and reproducible alternative to the bioassay for quality control and stability studies for rhbFGF-CS23 preparations. HA-HPLC is also considered to be applicable to assays for FGFs which have heparin affinity and biological activity similar to those of the CS23 mutein.

Animals↗

Noninvasive assessment of right heart function by 81mKr equilibrium radionuclide ventriculography in chronic pulmonary diseases.

Noninvasive multigated equilibrium radionuclide ventriculography with krypton-81m (81mKr) was used to assess right heart relaxation in patients with chronic pulmonary diseases (CPD). The subjects consisted of 30 patients with CPD and 8 patients free of cardiopulmonary diseases admitted to our department. A region of interest (ROI) was selected on both the right atrium (RA) and right ventricle (RV). A time activity curve was obtained for each ROI. As a diastolic index of the right heart performance, the right atrial early emptying rate (RAER) was obtained from the right atrial time activity curve, while the right ventricular rapid filling rate (RVRFR) was obtained from the right ventricular time activity curve. The mean RAER was significantly lower in CPD patients compared with the control (CPD, 9.5 +/- 4.5; control, 16 +/- 3.4%/100 ms). Similarly, the mean RVRFR was significantly lower in CPD patients compared with the control (CPD, 27.3 +/- 9.9; control, 34 +/- 8.5%/100 ms). A strong negative correlation was noted between the mean pulmonary arterial pressure (mPAP) and RAER (r = -0.77; p < 0.001) and between the mPAP and the RVRFR (r = -0.63; p < 0.001). Our results suggest that RAER and RVRFR measured by 81mKr are clinically useful in the noninvasive assessment of right heart relaxation in patients with CPD.

Adult↗

Iodine-123-metaiodobenzylguanidine myocardial imaging in patients with right ventricular pressure overload.

UNLABELLED: Iodine-123-metaiodobenzylguanidine ([123I]MIBG) has been used to evaluate the cardiac sympathetic nervous system, particularly that of the left heart. To clarify whether the right ventricular (RV) sympathetic neuronal function could be evaluated by [123I]MIBG myocardial imaging, we applied the technique in patients with pulmonary hypertension that was associated with either chronic pulmonary diseases or pulmonary vascular diseases. METHODS: All patients underwent right heart catheterization, and right heart hemodynamics were determined during a clinically stable state. SPECT was performed in the resting state 15 min (early imaging) and 4 hr (delayed imaging) postadministration of [123I]MIBG. Seven regions of interest (ROI) were selected on the delayed short-axis images on the RV free wall, left ventricular (LV) free wall and interventricular septum (IVS). We calculated the IVS-to-LV uptake ratio from the scintillation counts of the ROI. Thallium-201 myocardial imaging was also performed within 1 wk after [123I]MIBG imaging. RESULTS: Images obtained with these techniques were analyzed for the RV-to-LV uptake ratio. The IVS-to-LV ratio on [123I]MIBG correlated negatively and significantly with the mean pulmonary arterial pressure (PAm). The RV-to-LV uptake ratio on 201Tl images correlated significantly with PAm. CONCLUSION: Our results suggest that the uptake ratio of [123I]MIBG in the IVS is a useful index for evaluating the severity of pulmonary hypertension, and that chronic RV pressure overload contributes to disturbances of the cardiac sympathetic nervous system.

3-Iodobenzylguanidine↗

CD4+ T cells anergized by high dose feeding establish oral tolerance to antibody responses when transferred in SCID and nude mice.

The cellular mechanism for oral tolerance in specific Ab response was investigated by cell-transfer experiments, using severe combined immunodeficiency (SCID) and BALB/c nu/nu mice. High dose feeding with bovine alpha s1-casein, a major allergen in milk, to BALB/c mice induced Ag-specific oral tolerance to the specific Ab response. This state of oral tolerance was successfully transferred to SCID mice with splenocytes from orally tolerant BALB/c mice. In SCID mice that were transferred with tolerant T cells and normal B cells before being immunized with alpha s1-casein, oral tolerance to the Ab responses was generated. In addition, only the T cells established the tolerant state in nude mice. A decreased proliferative response of the splenic T cells from BALB/c mice against alpha s1-casein was also shown, indicating that the decreased Ab responses were attributed to the unresponsiveness of the splenic T cells. Next, the tolerant splenic T cells were further separated into CD4+ T cells and CD8+ T cells, remixed with normal cells, and then transferred to nude mice, which revealed that the tolerant state in the nude mice was principally generated by the CD4+ T cells. When tolerant CD4+ T cells were cotransferred with normal CD4+ T cells to nude mice, there was no significant reduction in the specific Ab responses. These results demonstrate that splenic CD4+ T cells anergized by high dose feeding established oral tolerance to the Ab responses when transferred to SCID and nude mice.

Administration, Oral↗

CD8+ T cells specific to the exogenous antigen. Mode of antigen recognition and possible implication in immunosuppression.

This study demonstrates and characterizes CD8+ T cells specific to the exogenous Ag, bovine alpha s1-casein. Purified CD8+ T cells from alpha s1-casein-primed lymph node cells proliferated well in response to an alpha s1-casein derivative, trypsin-digested alpha s1-casein. CD8+ T cell repertoire for the exogenous Ag was directly demonstrated in the primary culture condition. The intact alpha s1-casein primed the responding CD8+ T cells in vivo more efficiently than the tryptic alpha s1-casein; however, the in vitro proliferative response by the intact alpha s1-casein was weaker than that of the tryptic alpha s1-casein. CD8+ T cells recognized the exogenous Ag in association with MHC class I molecules as revealed by an Ab-blocking study. The major immunodominant region for the CD8+ T cells was mapped to region 136-151 of alpha s1-casein, and peptide 136-151 primed the responding CD8+ T cells but not any CD4+ T cells. Peptide 136-151 is the CD8+ T cell-specific determinant. Upon antigenic stimulation, the exogenous Ag-specific CD8+ T cells produced a significant level of IFN-gamma, which has immune suppressive activity for IgE synthesis. Our study strongly implies that CD8+ T cells that proliferate and produce IFN-gamma in response to the exogenous Ag would play a vital role in Ag-specific immunosuppression.

Age Factors↗

Dizocilpine (MK-801) elicits a tetrodotoxin-sensitive increase in extracellular release of dopamine in rat medial frontal cortex.

We have examined in the rat the effects of a selective non-competitive antagonist for the N-methyl-D-aspartate (NMDA) type excitatory amino acid receptor, dizocilpine (MK-801), on cortical dopamine (DA) metabolism using an in vivo dialysis technique. An acute intraperitoneal injection of MK-801 (0.4-1.25 mg/kg) dramatically increased the concentrations of dopamine, 3,4-dihydroxy-phenylacetic acid and homovanillic acid in the dialysates from the medial frontal cortex in a dose-dependent fashion. Moreover, MK-801 caused a delayed and small augmentation of the cortical extracellular release of 5-hydroxyindoleacetic acid. Continuous infusion of tetrodotoxin into the prefrontal region via the microdialysis tube completely blocked the ability of MK-801 (1.25 mg/kg, intraperitoneally) to augment the extracellular release of DA, its metabolites and the serotonin metabolite in the frontal cortex. The present results suggest that MK-801 facilitates DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area adding further support to the view that the NMDA receptor may be involved in the tonic inhibition of frontal cortical DA neurons. It is also proposed that frontal serotonin neurons might be under regulation by excitatory amino acidergic transmission via the NMDA receptor.

3,4-Dihydroxyphenylacetic Acid↗

Alpha s1-casein-specific CD8+ T cell clone that inhibits its own interferon-gamma production by producing interleukin-10.

A CD8+ T cell clone specific to alpha s1-casein, one of the major allergens in milk, is shown to inhibit its own production of interferon (IFN)-gamma by producing interleukin (IL)-10. Anti-IL-10 antibodies enhanced the production of IFN-gamma induced by the antigen plus antigen-presenting cells from 12 h onward after initiating the culture. This enhancing effect was observed only when the cells were stimulated in the presence of the antigen-presenting cells. Neither IL-2 nor IL-4 abrogated this enhancing effect. This reveals a new regulating mechanism for IFN-gamma production from CD8+ T cells.

Adjuvants, Immunologic↗

[Evaluation of the pulmonary vascular bed by digital subtraction angiography].

We studied the usefulness of digital subtraction angiography for evaluating the pulmonary capillary bed. Four individuals underwent the procedure. One was a healthy volunteer and the others were patients with chronic pulmonary emphysema. During catheterization, an 8 F balloon catheter was manipulated into the right pulmonary artery. A total of 20 ml of contrast material was injected at a rate of 10 ml/sec at full inspiration. In the normal subject, the capillary bed filled homogeneously and no defect was seen. In the patients, the pulmonary artery was nearly normal, but severe defects were observed in the pulmonary capillaries. Contrast resolvability was greater with digital subtraction pulmonary angiography than with pulmonary perfusion scintigraphy or pulmonary arteriography. This technique makes possible the visual evaluation of the pulmonary capillary bed.

Aged↗

c-Fos induction in the rat spinal dorsal horn partially deafferented by dorsal rhizotomy.

The 4th and 5th segments of the lumbar (the L4 and L5) dorsal horn receive primary input from the sciatic receptive fields through the L4 and L5 dorsal roots. Noxious stimulation of the hindpaw with formalin induces c-Fos in neurons in superficial laminae (I and II) of these dorsal horn segments. Rhizotomy of the L5 dorsal root 2 days before stimulation resulted in a marked reduction in the number of neurons with c-Fos protein-like immunoreactivity (fos-neurons). At 3 weeks after the L5 rhizotomy, the number of fos-neurons in laminae I and II significantly increased compared to that at 2 days post-rhizotomy. This result indicates that chronic partial deafferentation by dorsal rhizotomy increases responsiveness of superficial dorsal horn neurons to spared primary input.

Animals↗

Autoreactive CD8+ T cell clones producing immune suppressive lymphokines IL-10 and interferon-gamma.

Highly purified CD8+ T cells were stimulated repeatedly by syngeneic irradiated spleen cells. From separate cloning experiments, we succeeded in isolating two CD8+ clones, 4B4 and D2, which proliferated in response to autologous antigen-presenting cells (APC) completely in the absence of fetal calf serum. A T cell proliferation assay, using congenic strain of mice, indicates that both autoreactive clones were restricted to self-Db molecules. Our study is the first report of establishing murine autoreactive CD8+ clones restricted to self MHC class I molecules. To assess the immune suppressive activity of each autoreactive clone, we measured the production of IL-10 and interferon-gamma, which have specific immune suppressive activity toward type 1 helper T cell (Th1) proliferation and IgE synthesis, respectively. In response to autologous APC, both D2 and 4B4 produced considerable amounts of interferon-gamma and a low but significant level of IL-10. Each supernatant of D2 and 4B4 significantly suppressed IgE synthesis. These results strongly suggest the existence of CD8+ autoreactive T cells with immune suppressive activity.

Animals↗