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Biomedical subjects

I Iwamoto

Publications and source records attributed to I Iwamoto.

At least 145 records · Page 8Linked to original sources
PubMed1992

The in vivo depletion of CD4+ T cells prevents antigen-induced eosinophil infiltration into mouse skin.

In order to determine the role of CD4+ T cells and CD8+ T cells in causing antigen-induced eosinophil infiltration into the site of late-phase reaction (LPR), we examined the effect of the in vivo depletion of CD4+ T cells and CD8+ T cells on antigen-induced eosinophil infiltration into mouse skin. Eosinophil infiltration into the skin of ovalbumin (OA)-sensitized BALB/c mice was biphasic after subcutaneous OA challenge, reaching the first peak at 6 h and the second peak at 24 to 48 h. The in vivo depletion of CD4+ T cells by pretreatment with anti-L3T4 monoclonal antibody (mAb) significantly decreased the second peak (at 24 h and 48 h), but not the first peak (at 6 h), of OA-induced eosinophil infiltration into the skin of OA-sensitized mice. However, the depletion of CD8+ T cells by pretreatment with anti-Lyt-2 mAb had no significant effect on either the first or second peak of OA-induced cutaneous eosinophilia in the mouse. These results indicate that CD4+ T cells, but not CD8+ T cells, play an important role in causing antigen-induced eosinophil recruitment of cutaneous LPR.

Animals↗
PubMed1992

[The potencies of substance P, substance P fragments, and compound 48/80 for granulocyte infiltration in mouse skin].

To determine whether the N-terminal or C-terminal peptide of substance P (SP) induces granulocyte infiltration in mouse skin, we examined the potencies of SP, the N-terminal peptides SP1-4 and SP1-9, the C-terminal peptides SP4-11 and SP6-11, and a mast cell degranulating agent compound 48/80 in inducing granulocyte (neutrophil and eosinophil) infiltration in the skin of BALB/c mice. The subcutaneous administration of SP (10(-7)-10(-5) M) caused granulocyte infiltration in mouse skin in a concentration-dependent fashion 6 h after the injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration in the skin which was associated with mast cell degranulation. However, SP1-4, SP4-11 and SP6-11 (up to 10(-4) M) induced neither granulocyte infiltration nor mast cell degranulation. In addition, compound 48/80 (0.5-50 micrograms/ml) also induced granulocyte infiltration of mouse skin with a concentration-dependent increase in mast cell degranulation. These results indicate that SP induces granulocyte infiltration of mouse skin through mast cell degranulation induced by the N-terminal peptide.

Animals↗
PubMed1992

[Studies on pseudo-Chediak-Higashi granules formation in acute promyelocytic leukemia].

Leukemic cells from acute promyelocytic leukemia containing pseudo-Chediak-Higashi (P-CH) granules in a 38-year-woman were studied with ultrastructural and cytochemical techniques to evaluate the origin and nature of the granules. Wright-Giemsa stain revealed giant granules to be azurophilic. Cytochemical stain revealed p-CH granules ot the basic of their peroxidase and glycoprotein content. Electron microscopy revealed numerous giant granules formed by fusion of azurophilic granules these morphological, different type granules were classified into four types, 1) circular granule with homogeneous matrix, 2) circular granule with heterogeneous change by autolysis, 3) Auer body-like granule with crystalline arrangement, 4) vacuolar formation. The results demonstrate that the Auer body-like granule of P-CH granules in leukemic cells is a morphologically variant type of the classical Auer body observed in common acute myeloid leukemia.

Adult↗
PubMed1991

Distribution of neutral endopeptidase activity in human blood leukocytes.

We investigated the distribution of neutral endopeptidase (NEP; EC 3.4.24.11) activity, a possible regulatory enzyme for neuropeptide-induced leukocyte activations, in each cell type of human blood leukocytes. The NEP activity assessed by an NEP inhibitor phosphoramidon-sensitive Met5-enkephalin degrading activity was present in neutrophils and the common acute lymphoblastic leukemia antigen (CALLA)-positive leukemic cells (59 pmol/min/10(6) cells and 62 pmol/min/10(6) cells, respectively); however, the NEP activity was virtually absent in lymphocytes, monocytes, eosinophils, basophils, CALLA-negative leukemic cells, or a promyelocytic cell line HL-60. The enzymatic activity was characterized as NEP on the basis of the values of kinetic parameters (Km = 61 microM, Kcat = 1,692 min-1, and Kcat/Km = 28 min-1 microM-1) and the values of IC50 of two NEP inhibitors phosphoramidon and thiorphan (7.4 nM and 8.4 nM, respectively). The distribution of NEP detected immunocytochemically using anti-NEP monoclonal antibodies was also found to be parallel with the distribution of NEP activity among peripheral blood leukocytes.

Basophils↗
PubMed1991

Neutral endopeptidase (EC 3.4.24.11) does not hydrolyze recombinant human interleukin-1 beta.

We have previously shown that neutral endopeptidase (NEP; EC 3.4.24.11) regulates neuropeptide-induced responses. Recently, Pierart et al. reported that NEP degraded purified interleukin-1 (IL-1) using thymocyte proliferation assay. Since IL-1 is an important cytokine in the immune response and inflammation, we have assessed whether NEP hydrolyzes recombinant human IL-1 beta using three assay systems (bioassay, immunoassay, and HPLC analysis). NEP on the NALM-6 cells (both intact cells and the solubilized plasma membrane fraction) efficiently hydrolyzed Met5-enkephalin and substance P. However, NEP did not significantly decrease the amount of rhIL-1 beta assessed by the growth inhibitory activity of a human melanoma, by the immunoassay, or by the direct analysis on HPLC. Therefore, we conclude that NEP does not significantly hydrolyze rhIL-1 beta. Our results suggest that, in contrast to the regulatory role of NEP in neuropeptide-induced responses, NEP is not a regulatory enzyme for IL-1-induced responses.

Enkephalin, Methionine↗
PubMed1991

Characteristics of an anti-eosinophil monoclonal antibody that recognizes granulocytes from patients with blood eosinophilia but not from subjects without eosinophilia.

To investigate cell surface antigens of activated human eosinophils using monoclonal antibodies, we established a murine anti-human eosinophil monoclonal antibody AE500 by immunizing with blood eosinophils from patients with idiopathic hypereosinophilic syndrome (HES) and characterized the reactivity to a variety of human leucocytes by a fluorescence-activated cell sorter. AE500 reacted with blood eosinophils and neutrophils in nine out of 11 patients with marked eosinophilia (greater than or equal to 2500/microliters) (seven with idiopathic eosinophilia including HES and two with asthma), but not with those in asthmatic patients with mild eosinophilia (n = 10) or in healthy subjects (n = 8). AE500 did not react with blood lymphocytes, monocytes or platelets. AE500 did not react with human myeloid or lymphoid cell lines, including eosinophilic leukemia cell lines EOL-1 and EOL-3. The reactivity of AE500 to blood eosinophils and neutrophils in patients with marked eosinophilia changed in relation to blood eosinophil counts and prednisolone therapy. In addition, the reactivity of AE500 to blood eosinophils was increased in three out of four AE500-positive eosinophils by the incubation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) at 37 degrees C for 30 min, but not with interleukin 3 or interleukin-5. These results suggest that the anti-eosinophil antibody AE500 detects a cell surface antigen expressed on blood granulocytes in a hypereosinophilic state. This anti-eosinophil antibody would be useful for analysing the mechanism of eosinophilia.

Antibodies, Monoclonal↗
PubMed1991

Inhibitory effect of tranilast on substance P-induced plasma extravasation in rat skin.

The effect of tranilast, an inhibitor for IgE-mediated mediator release from mast cells, on plasma extravasation induced by the intradermal injection of substance P in rats was examined. Tranilast (100 mg/kg, intraperitoneally) decreased plasma extravasation induced by substance P (10(-7)-10(-5) M). Tranilast decreased plasma extravasation induced by the amino-terminal peptide substance P1-9 (10(-6)-10(-4) M), which is active for rat mast cells, but not by the carboxy-terminal peptide substance P6-11 (10(-6)-10(-4) M), which is inactive for the mast cells. Therefore, tranilast prevents substance P-induced plasma extravasation most likely by inhibiting mast cell degranulation.

Animals↗
PubMed1991

[Pharmacokinetics of cefodizime in patients undergoing hemodialysis].

The object of this study was to establish the most effective regimen of cefodizime (CDZM) for patients with chronic renal failure undergoing hemodialysis (HD). T 1/2 beta of CDZM upon 1 g intravenous administration was 3.50 +/- 0.72 hours in an on-HD group, and it was 11.26 +/- 3.89 hours in an off-HD group. When CDZM was administered consecutively at a dose of 1 g or 2 g only after HD, the serum concentration of CDZM was maintained at levels sufficient to exert antibacterial activity, and no tendency for accumulation was observed. The most effective regimen of CDZM to HD patients, therefore, has been that in which concluded to administration was done only after completion of HD, in a dose of 1 g for mild infections and that of 2 g for severe infections.

Cefotaxime↗
PubMed1991

[Methods of anesthesia in canine heart-lung transplants].

Hypothermia has many valuable merits compared with under cardiopulmonary bypass using pump oxygenator, as known. But, on the contrary, it has some weak points, such as, long time required for cooling and rewarming. We have developed the device for rapid cooling and rewarming by using jet water blows. It appeared that the key point in hypothermia was control of ether inhalation and timing of rewarming. We demonstrated that mongrel dog could survive for at least 72 hours after transplantation of heart-lung under simple deep hypothermia with ether anesthesia. The dog was breathing 50-100 percent oxygen gas under control through respiratory ventilator. Postoperative arterial blood gases were maintained between pH 7.3-7.5 and PO2 80-200mmHg on the other hand, PCO2 was unstable from 14 to 63mmHg. It seemed that the anesthesia in canine heart-lung transplants using profound surface hypothermia with either anesthesia was useful methods.

Anesthesia, Closed-Circuit↗
PubMed1990

The relation between EEG and mental development following cardiac surgery performed under simple deep hypothermia in children.

In order to assess the accuracy of electroencephalography (EEG), in children who have undergone cardiac surgery under simple deep hypothermia, the relation between IQ or schoolwork achievement and the duration of circulatory arrest was investigated in 75 such children. Abnormal preoperative EEG's were found in 16 per cent of the children while abnormal postoperative EEG's were found in 17 per cent. The children were divided into 4 groups, according to pre- and postoperative EEG results. Schoolwork achievement scores ranged between 3.0 and 3.2, the difference among the groups being insignificant. Moreover, no significant shift in IQ was found among the groups. Finally, regarding the number of children who were able to go on to a higher level of education, including high school then college or university, again no significant differences were found among the 4 groups. In a comparison with the number of such children in neighboring Nagasaki prefecture able to continue on to a higher level of education, no significant differences were seen either. The findings and statistics of this investigation therefore indicate that pre- and postoperative EEG's are not always a reliable reference for assessing the prognosis of cerebral activity.

Achievement↗
PubMed1990

Differential effects of two C-terminal peptides of substance P on human neutrophils.

To determine the mechanism by which substance P (SP) activates human neutrophils, we examined the potencies of SP, the C-terminal peptides SP4-11 and SP6-11, and the N-terminal peptides SP1-9 and SP1-4 for inducing the increase in cytosolic free Ca2+ concentration ([Ca2+]i), superoxide (O2-) generation, and chemotaxis in human blood neutrophils. SP and the C-terminal peptides SP4-11 and SP6-11 and SP6-11 (10(-6)-10(-4) M) induced the increase in ([Ca2+]i, O2- generation, and chemotaxis of the neutrophils dose--dependently, whereas the N-terminal peptides SP1-9 and SP1-4 (up to 10(-4) M) were inactive in inducing these responses. Furthermore, the potencies of the two C-terminal peptides SP4-11 and SP6-11 were not parallel in these three responses. SP6-11 was 7.7-fold more potent in increasing [Ca2+]i than SP4-11, whereas SP4-11 was 16.6-fold more potent in inducing O2-generation than SP6-11. SP6-11 was also 2.1-fold more potent in inducing chemotaxis than SP4-11. Thus, we conclude that the C-terminal peptides of SP induce differential activations of human neutrophils.

Calcium↗
PubMed1990

Comparison of a multi-allergen dipstick IgE assay to skin-prick test and RAST.

A multi-allergen dipstick enzyme immunoassay 'Quidel Allergy Screen' (QAS) has recently been developed commercially for measuring IgE antibodies against nine allergens (house dust 1, house dust 2, Dermatophagoides pteronyssinus, D. farinae, Japanese cedar, ragweed, cat dander, sweet vernal grass, and egg white) at one time. To assess whether this assay is useful in screening allergen-specific IgE antibody, we compared the titres of IgE antibodies against the nine allergens measured by QAS to those in the skin-prick test and by RAST in 93 atopic asthmatics and 22 normal subjects. We found a good overall agreement between the results of the skin-prick test and the results of QAS (sensitivity = 47.1-81.4%, specificity = 84.5-100%, and agreement = 78.9-88.9%). The sensitivities against house dust 1, D. pteronyssinus, and D. farinae ranged from 77.2 to 81.4%. However, the sensitivities against house dust 2, Japanese cedar, ragweed, and cat dander were low (47.1-68.8%). We also found a good overall agreement between the results of RAST and the results of QAS, except for egg white (sensitivity = 46.2-94.4%, specificity = 87.4-100%, and agreement = 77.4-96.5%). The sensitivities against house dust 1 and 2, D. pteronyssinus, D. farinae, and Japanese cedar ranged from 86.0 to 94.4%. The sensitivities against ragweed, cat dander, and sweet vernal grass were low (46.2-52.6%). There were strong correlations between the titres of RAST and the titres of QAS except cat dander and egg white (r = 0.701-0.924 for the seven allergens). Thus, we conclude that QAS is useful in screening IgE antibodies against multiple allergens at one time. However, because the sensitivities against some allergens tested were low, further improvement of some allergen preparations seems to be necessary in the assay.

Adolescent↗
PubMed1990

Recombinant neutral endopeptidase attenuates substance P-induced plasma extravasation in the guinea pig skin.

To determine whether exogenously administered neutral endopeptidase (NEP; enkephalinase, EC 3.4.24.11) inhibits the substance P-induced increase in vascular permeability in the skin, we examined the effects of recombinant human NEP on plasma extravasation induced by intradermal injection of substance P in guinea pig skin. Injection of substance P (2.5 X 10(-8) M) induced significant plasma extravasation in the skin (53 +/- 4 mm2 of Evans blue extravasation; mean +/- 1 SEM). In vitro incubation of substance P with recombinant human NEP prior to injection prevented the substance P-induced plasma extravasation in the skin in a dose-dependent fashion. Intradermal preinjection of recombinant human NEP partially inhibited plasma extravasation induced by subsequent injection of substance P (52 +/- 9% of the control without NEP). The H1 and H2 histamine antagonists pyrilamine and cimetidine, and a muscarinic antagonist, atropine, had no effects on substance P-induced responses. Two products of substance P degradation by NEP containing the carboxy-terminal portion, substance P7-11 and substance P8-11, were also without effect. These findings suggest that recombinant human NEP can attenuate substance P-induced increases in vascular permeability in guinea pig skin and, therefore, may be useful in treating dermatologic disorders in which abnormal responses to substance P or other neuropeptides cleaved by NEP may occur.

Animals↗
PubMed1990

Skin reactivity to substance P, not to neurokinin A, is increased in allergic asthmatics.

The tachykinins substance P (SP) and neurokinin A are believed to be major mediators of neurogenic inflammation. To determine whether the skin reactivity to tachykinins is increased in asthmatics, we examined the erythemas and wheals induced by intradermal injections of SP, the C-terminal peptide SP6-11, the N-terminal peptide SP1-9 and neurokinin A (10(-7)-10(-5) M) in 10 allergic asthmatics and 9 normal subjects. SP and SP1-9 induced both erythemas and wheals in a concentration-dependent manner in allergic asthmatics and in normal subjects, whereas SP6-11 and neurokinin A induced only wheals in both groups. SP induced greater erythemas and wheals in allergic asthmatics than in normal subjects. However, the wheals induced by neurokinin A were not significantly different between the two groups. SP1-9 also induced greater erythemas and wheals in allergic asthmatics than in normal subjects, whereas the wheals induced by SP6-11 were not significantly different between the two groups. Therefore, the increased skin reactivity to SP was dependent on the N-terminal peptide but not on the C-terminal peptide. We conclude that the skin reactivity to SP but not to neurokinin A is increased in allergic asthmatics.

Adult↗
PubMed1990

Neutral endopeptidase modulates substance P-induced activation of human neutrophils.

Neutral endopeptidase (NEP; EC 3.4.24.11) is well recognized as a regulatory peptidase for substance P (SP)-induced responses in various tissues. To determine whether NEP regulates SP-induced activation of human neutrophils, we examined the effect of the NEP inhibitor phosphoramidon on SP-induced superoxide generation and chemotaxis in human blood neutrophils. SP (10(-6)-10(-4) M) induced superoxide generation and chemotaxis in the neutrophils dose dependently. The NEP inhibitor enhanced the SP-induced responses. Thus, phosphoramidon (10(-6) M) shifted the dose-response curves of SP-induced superoxide generation and chemotaxis of the neutrophils to the left by 0.5-0.6 log. Phosphoramidon prevented the hydrolysis of SP by the neutrophils, the NEP activity of the neutrophils being assessed as 125 +/- 13 pmol of SP/min/10(6) cells. The N-terminal peptide SP (up to 3 x 10(-4) M), which was a major degrading product by NEP of the neutrophils, did not activate the neutrophils. We conclude that NEP modulates SP-induced activation of human neutrophils.

Humans↗