[Animal disease model of vasculitis--immune complex and host factors].
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Biomedical subjects
Publications and source records attributed to M Nose.
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Adenosine and its analogs (-)-N6-phenylisopropyladenosine and 5'-N-ethylcarboxamideadenosine inhibit cAMP and cGMP phosphodiesterase activity in guinea-pig atrial and ventricular preparations at concentrations of 100 mumol l-1 and higher. These effects are probably unrelated to the inotropic effects of these substances. However, inhibition of cAMP breakdown may compensate for the adenosine-induced inhibition of adenylate cyclase and may thus at least partially explain why with this drug no changes in cAMP or cGMP content have previously been observed in intact cardiac tissue.
We have investigated lectin-binding profiles of the human breast epithelia and the structural atypism in intraductal carcinoma. The lectino-histochemical probes using biotin-labeled peanut agglutinin (PNA), soybean agglutinin (SBA) and wheat germ agglutinin (WGA) with avidin-biotin peroxidase complex were performed on formalin-fixed and paraffin-embedded specimens from 24 patients. While normal and benign hyperplastic epithelia were stained almost in luminal borders and apical cytoplasmic surfaces, intraductal carcinoma additionally showed conspicuous staining of intracytoplasmic lumina and supranuclear cytoplasmic margins. The lectin-binding pattern found in papillary hyperplasia was completely different from that in intraductal carcinoma; the former was an irregular network structure along luminal borders, whereas the latter was not only a cribriform but also a rosette structure along intracytoplasmic lumina and supranuclear cytoplasms. Such lectin-binding patterns seemed to reflect the change of cell polarity in malignant transformation. The significance of these observations in elucidation of structural atypism was discussed in relation to 3-D structure of intraductal carcinoma.
We have prepared monoclonal hapten-specific mouse IgG2b antibodies depleted of asparagine-linked carbohydrate chains by treating the hybridoma cells with tunicamycin. The carbohydrate-deficient antibodies behaved in an identical manner to the normal antibodies with regard to fine antigen-binding reactivity (a Fab fragment feature) and protein A binding capacity [a feature requiring integrity at the CH2 and CH3 domain-interaction regions in the constant region of the heavy chain (CH)]. However, they lost the ability to activate complement, to bind to Fc receptors on macrophages, and to induce antibody-dependent cellular cytotoxicity. Furthermore, antigen-antibody complexes produced from such carbohydrate-deficient antibodies failed to be eliminated rapidly from the circulation. We conclude that removal of carbohydrate chains from IgG molecules may have a profound and highly select impact on the biological activity to these antibodies.
A murine-cultured lymphocytic leukemic cell line, SC-1, showed remarkable cytotoxicity against 51Cr-labeled rabbit erythrocytes as target cells in the presence of antitarget antibodies in vitro. This cytotoxicity was complement independent, inhibited by the addition of aggregated human gamma-globulin, and reduced by pepsin digestion of antitarget IgG. Moreover, SC-1 cells also induced cytotoxicity to trinitrophenyl-modified rabbit erythrocytes in the presence of antitrinitrophenyl antibodies but not unmodified rabbit erythrocytes used as bystander cells. SC-1 cells which showed such K cell activity, however escaped from Fc receptor detection by erythrocyte antibody rosettes and FITC-conjugated aggregated human gamma-globulin binding. In morphological studies using the scanning electron microscope, SC-1 cells to induce cytotoxicity through a light attachment to target cells via 'point contact' of the microvilli. From these findings the characteristics of Fc receptors on effector cells in the mechanism of antibody-dependent cellular cytotoxicity was discussed.
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A new sensitive and simplified method for detecting concanavalin A-induced cellular cytotoxicity was developed by using 51Cr-labeled rabbit erythrocytes as target cells, and a soluble cytotoxic factor (SCF) to rabbit erythrocytes was demonstrated with this system. From morphological studies, this factor appeared to play a major role in cellular cytotoxicity. The cytotoxic activity of SCF was removed by absorption with rabbit erythrocytes. Furthermore, the target cells pretreated with SCF and washed were subsequently destroyed. These results may indicate that SCF exerts its effect through binding to cellular receptors. Some monosaccharides showed inhibitory effects on the cytolysis of rabbit erythrocytes by SCF and on the adsorption of SCF activity to them. The significance of these findings in elucidation of the action of SCF was discussed.
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The mode and degree of tissue specific immunocytolysis closely depend on the nature of cell-surface antigens and on the competition or balance of humoral and cell-mediated immunity. The modification of cell surface membrane by neuraminidase-treatment induced the higher susceptibility to complement-dependent cytolysis, probably on account of exposure of cryptic sites or aggregation (clustering) of sites which may be tissue specific and/or histocompatibility antigen determinants. Under the existence of large amount of antisera, complement-dependent cytolysis was dominant. On the contrary, under the situation of low dose anti-sera, normal adherent-cell-mediated cytolysis was more effective. This kind of cytolysis was inhibited easily by serum factor(s), which could be IgG, and block Fc receptor of adherent cells in competition with anti-Ig14. Although the role of serum-factor(s) is still unknown, it may act an important role in the process of establishment of autoimmune diseases.
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The nasal mucociliary clearance was measured in 71 subjects with nasal allergy (NA) (56 subjects without sinusitis and 15 with sinusitis), 12 subjects with bronchial asthma (BA) (7 without, 5 with) and 7 subjects with aspirin-induced asthma (AIA) using a saccharin test. The results were compared with those obtained in a control group of 15 healthy subjects. The saccharin time (ST) values for both NA and BA subjects without sinusitis (16.9 +/- 9.9 and 20.1 +/- 9.4 min, respectively) did not differ from that of the healthy subjects (16.3 +/- 5.3 min). However, ST values in NA and BA subjects with sinusitis (37.6 +/- 22.9 and 57.0 +/- 6.7 min, respectively) were significantly higher than those of healthy subjects (p < 0.01). The ST value of AIA subjects (13.0 +/- 5.4 min) showed no significant difference compared with that of the control group. These results suggest that allergic reactions do not influence the nasal mucociliary clearance and that the property of mucus complicated with sinusitis is important. Also, sinusitis observed in AIA may be somewhat different from ordinary sinusitis complicated with NA and BA.
Bone formation is under the control of cytokines as well as growth factors such as bone morphogenetic proteins (BMP). This suggests the possibility that osteogenesis might be modulated by factors which also modulate the immune system. To test whether immune disorders in the host may influence bone formation, we studied BMP-induced bone formation in a C3H/HeJ strain of mice bearing a mutant gene, the lymphoproliferation gene (lpr) or the generalized lymphoproliferative disease gene (gld), both of which are known to be a Fas deletion mutant and a Fas ligand mutant, respectively, and to induce immune disorders via a deficit in Fas-mediated apoptosis. Crude BMP derived from bovine bone were injected into the muscular tissue in the femur of adult C3H/HeJ mice or C3H/HeJ mice bearing an lpr or gld gene. Quantitative analysis of the resulting ectopic bone formation by X-ray photography 2 weeks after injection revealed that the presence of either the lpr or gld gene caused a bone mass significantly larger in dimension than that seen in the wild type mice. Histological examination also revealed the different influence between these mutant genes on the level of bone formation exhibited by hyaline cartilage and bone trabeculae. Based on these results, we discussed the possible mechanisms of the enhanced ectopic bone formation under the deficit in Fas-mediated apoptosis.