PubMed Health⌕ Search

Biomedical subjects

M Nose

Publications and source records attributed to M Nose.

At least 181 records · Page 10Linked to original sources
PubMed1988

Complement activation is not required for IgG-mediated suppression of the antibody response.

Feedback suppression of the antibody response by IgG is known to be dependent on intact Fc regions. However, it is not clear which of the Fc-mediated effector functions is required. In the present report we have studied whether ability or inability of the IgG antibodies to activate the complement system was of consequence for their immunosuppressive effect. First, a monoclonal IgG1-anti-2,4,6-trinitrophenyl (TNP) antibody, unable to activate complement via the classical or alternate pathway, was shown to be able to inhibit more than 90% of the in vivo sheep erythrocyte-specific antibody response in mice when TNP coupled to sheep erythrocytes was used as antigen. Second, we investigated the immunosuppressive ability of a non-complement-activating mutant IgG2a-anti-TNP monoclonal antibody. The mutant differs from the wild type by a single amino acid substitution in the CH2 domain leading to inability to fix complement factor C1q. However, the mutant has the same affinity for antigen and the same Fc receptor-binding capacity as the wild type antibody. It is demonstrated that the mutant was as efficient as the wild type antibody in inhibiting an in vitro antibody response to TNP-coupled sheep erythrocytes. These findings confirm the non-determinant specificity and Fc dependence of IgG-mediated suppression, and show that the Fc-mediated effector mechanism is independent of complement activation. The results instead suggest binding to Fc receptors as a necessary step in feedback immunosuppression and favor inactivation of B cells by cross-linking of Fc and antigen receptors on their surface rather than elimination of antigen by complement-dependent phagocytosis as the effector mechanism.

Animals↗
PubMed1988

Features of the in vitro established rat large granular lymphocyte leukaemia RNK-16.

A large granular lymphocyte (LGL) leukaemia cell line from the Fisher/F344 rat strain called RNK-16 has been established in vitro, maintaining the same surface markers as tumour cell growing in vivo. The tumour has also maintained its specificity pattern and cytotoxic reactivity and serves as a suitable source of natural killer (NK)-like effector cells in vitro. The cells show no evidence of dependency on, or production of, interleukin 2 or interferons, nor is the cytotoxic capacity influenced by treatment with mitogens. The in vitro line does not produce natural killer cytotoxic factor (NKCF) in a constitutive manner, but can be induced to do so via coculture with tumour target cells. When the fine specificity patterns were analysed, the RNK-16 cells express species-preferential lysis of susceptible target cells and a highly discriminatory power to kill only 1 out of 5 rat erythroleukaemia cell lines. When testing normal target susceptibility patterns, RNK-16 kills lymphoblasts of B type better than T blasts, which is well in line with previous findings on normal NK cell specificity patterns.

Animals↗
PubMed1988

Adenosine inhibits the positive inotropic effect of 3-isobutyl-1-methylxanthine in papillary muscles without effect on cyclic AMP or cyclic GMP.

1 Adenosine and the adenosine receptor agonist (-)-N6-phenylisopropyladenosine (PIA) produced a small positive and negative inotropic effect, respectively, in isolated electrically driven papillary muscles of guinea-pigs. 2 Adenosine (100 mumol l-1) had no effect on cyclic AMP or cyclic GMP content. PIA (100 mumol l-1) slightly increased cyclic AMP. 3 In the presence of 3-isobutyl-1-methylxanthine (IBMX; 60 mumol l-1), which increased force of contraction 2 fold, adenosine and PIA exerted strong negative inotropic effects. PIA was more potent than adenosine (mean IC25 2.1 and 168 mumol -1, respectively). 4 In contrast, the nucleosides did not affect the increase in force of contraction produced by elevating extracellular Ca2+ concentration. 5 The IBMX-antagonistic effects of adenosine and PIA were not accompanied by modification of the IBMX-induced increase in cyclic AMP and cyclic GMP. 6 The effects of adenosine and PIA on force of contraction were accompanied by a partial reversal of the IBMX-induced increase in the maximal rate of depolarization of slow action potentials. 7 It is concluded that adenosine and PIA are able to attenuate the positive inotropic effect of a phosphodiesterase inhibitor. This effect is unlikely to be due to a reduction of the IBMX-induced increase in cyclic AMP content. It is conceivably due to an inhibition of the stimulant action of cyclic AMP on slow Ca2+ channels leading to the reduction of the slow inward current which in turn reduces force of contraction.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Pathogenesis of arteritis of SL/Ni mice. Possible lytic effect of anti-gp70 antibodies on vascular smooth muscle cells.

The SL/Ni strain of mice spontaneously develops a necrotizing polyarteritis (NPA) that is histologically quite similar to human polyarteritis nodosa. This NPA most frequently affected parametrial tissues and/or ovaries of females and small arterioles of the major salivary glands. Electron microscopic studies of early arterial lesions revealed massive budding of C-type particles from arterial smooth muscle cells just before or at the onset of arteritis. In addition, binding of mouse IgG and C3 to the plasma membrane of virus-producing smooth muscle cells was shown by immunoelectron microscopy. Antibody-bound muscle cells showed disintegration of their plasma membrane, but degeneration and necrosis of muscle cells were not associated with dense infiltration of neutrophils. SL/Ni mice had natural antibodies that bound specifically to a fibroblast cell line infected with an endogenous ecotropic murine leukemia virus (MuLV) recovered from a SL/Ni mouse. Most of the natural antibodies were cytotoxic in the presence of murine complement. Western blot immunoassays revealed that among 14 SL/Ni female mice tested, all of the 9 mice that were affected by arteritis had anti-gp70 antibodies, while the 3 anti-gp70- mice were not affected. The presence of anti-p30 or anti-p15 (anti-p12) antibodies, which were also detected in some SL/Ni mice, did not correlate with the development of arteritis. These results strongly support the hypothesis that NPA in SL/Ni mice is mediated by the lysis of arterial smooth muscle cells due to the deposition of cytotoxic natural antibodies directed to cell membrane-bound gp70 molecules of an endogenous ecotropic MuLV.

Animals↗
PubMed1987

Differential expression of carcinoembryonic antigen in early gastric adenocarcinomas versus benign gastric lesions defined by monoclonal antibodies reactive with restricted antigen epitopes.

Murine monoclonal antibodies (MAbs) reactive with distinct epitopes on carcinoembryonic antigen (CEA) have been analyzed systematically by radioimmunoassays, Western blotting, and immunohistochemical assays to define CEA expression in adenocarcinomas, benign lesions, and normal tissues of the stomach. Each of four COL-MAbs (COL-1, COL-4, COL-6, and COL-12) reacted preferentially with cell extracts of adenocarcinomas versus those of normal mucosae in solid-phase radioimmunoassays. Using Western blotting analyses MAbs COL-1, COL-4, COL-6, and COL-12 detected only the Mr 180,000 molecule characteristic of CEA in adenocarcinoma of the stomach; no reactivity was observed in an extract of normal gastric mucosa. Antibody competition radioimmunoassays were then carried out to define relations among COL-MAbs using 125I-radiolabeled MAbs, and nonradiolabeled MAbs as competitors. A spectrum of formalin-fixed, paraffin-embedded normal, benign, and malignant tissue sections of the stomach were examined for immunoreactivities with COL-MAbs using immunohistochemical assays to define whether the COL-MAbs were able to detect CEA expression in early foci of gastric carcinomas. All of the COL-MAbs generally demonstrated selective reactivities to adenocarcinomas (n = 40) versus benign lesions (n = 15) and normal mucosae (n = 6) of the stomach. From 72 to 100% of adenocarcinomas at early stage (n = 18) were reactive with the COL-MAbs, suggesting that these MAbs might serve as immunohistochemical diagnostic tools to detect early foci of gastric carcinoma. The data reported here indicate that the COL-MAbs can potentially be utilized as radioimmunological and immunohistochemical adjuncts to differentiate early adenocarcinomas from normal mucosae or benign lesions of the stomach on the basis of differential CEA expression.

Adenocarcinoma↗
PubMed1987

Enhanced expression of c-Ha-ras p21 in human stomach adenocarcinomas defined by immunoassays using monoclonal antibodies and in situ hybridization.

Using c-Ha-, c-Ki-, and c-N-ras-specific probes in a RNA-RNA hybridization assay we found enhanced expression of c-Ha-ras protooncogene in stomach adenocarcinomas relative to nonneoplastic epithelium, whereas little or no transcription of either c-Ki- or c-N-ras was detected. Enhanced levels of c-Ha-ras RNA expression were detected in all of the adenocarcinomas examined. Hybridization with c-Ha-ras was also detected in nonneoplastic gastric epithelium adjacent to carcinoma, although the labeling was less intense than that of carcinoma cells. More extensive analysis of the c-Ha-ras p21 expression was then carried out in formalin-fixed, paraffin-embedded tissue sections and extracts from surgically resected stomach tissues using monoclonal antibodies (MAbs) RAP-5 and Y13-259. The data obtained from the immunohistochemical studies were consistent with the results of in situ hybridization assay. Adenocarcinomas were much more reactive with MAb RAP-5 than benign and normal tissues, and the majority of carcinomas demonstrated increased expression of c-Ha-ras p21. Quantitative liquid competition radioimmunoassays using MAb Y13-259 also demonstrated significantly higher levels of c-Ha-ras p21 in extracts from stomach adenocarcinomas than those from normal mucosae. No strict correlation was found between ras p21 expression and the degree of tumor differentiation or histological type. Although advanced carcinomas generally demonstrated higher levels of ras p21 than early carcinomas, no correlation among advanced carcinomas and ras p21 levels was observed in relation to depth of tumor invasion to the muscularis propria, subserosa, or serosa. Benign lesions, in comparison, were much less reactive with MAb RAP-5 than carcinomas. Among the benign lesions tested, dysplastic lesions were more reactive than nondysplastic lesions. Normal stomach mucosa was generally nonreactive with the exception of parietal cells. Our results indicate that transformation of the stomach mucosa from benign to malignant phenotype is associated with an increase in c-Ha-ras p21 expression.

Adenocarcinoma↗
PubMed1987

The effect of tunicamycin on target cell susceptibility to natural killer cell cytotoxicity.

Several sets of data indicate the possibility that carbohydrate moieties on the target cell are important structures in natural killer (NK) cell-mediated lysis. Striking changes in the NK susceptibility of targets can be induced in several systems involving in vitro differentiation of tumour cell lines. The effect on target cells of the glycosylation inhibitor tunicamycin, which acts by blocking the dolichol-dependent asparagine-linked glycosylation pathway was investigated. Using several different tumour cell lines we can conclude that: asparagine-linked carbohydrate chains do not contribute directly to NK susceptibility, induced differentiation may or may not be linked with a change in NK susceptibility, and secondary changes caused by tunicamycin treatment may lead to alterations in the gangliosides, a finding that is positively correlated with decreased NK susceptibility.

Animals↗
PubMed1987

Immunopathology of murine lupus-overview, SL/Ni and MRL/Mp-lpr/lpr-.

Murine lupus is a useful animal model for the study of disease based on some defect in the immune system including the so-called collagen diseases. Seven strains are available in Japan; NZB, NZB/WF1, MRL/Mp-lpr/lpr, BxSB, SL/Ni, NC and C3H/HeJ-gld/gld. Characteristics of these strains of mice are outlined. Care should be taken about applying the knowledge or information obtained from animal models to the analysis of related human disease because there are various genetic or species barriers which cannot be overcome. Therefore, it is rather dangerous to conclude that the pathogenesis of some human disease is similar to that of an animal model from a study of the latter. Therefore, one should divide the data obtained from animal experiments into "factors" and insert each factor in the "formula" of a human disease in order to better understand it. Recent studies by the authors on two strains of lupus mouse; SL/Ni and MRL/Mp-lpr/lpr from such a standpoint are presented and discussed in detail.

Animals↗
PubMed1986

Tumor-associated glycoprotein (TAG-72) detected in adenocarcinomas and benign lesions of the stomach.

Murine monoclonal antibody (MAb) B72.3, prepared against a membrane-enriched extract of metastatic carcinoma and reactive with a high-molecular-weight determinant, designated tumor-associated glycoprotein (TAG)-72, was shown to be reactive immunohistochemically with 97% of a variety of primary adenocarcinomas of the stomach (n = 40). All "early" gastric carcinomas were reactive with MAb B72.3, although the average percentage cellular reactivity was lower than in "advanced" carcinomas. TAG-72 antigen was detected in benign lesions (i.e. adenomatous polyps and hyperplastic polyps) with intestinal metaplasia. Dysplastic lesions characterized by cellular atypia, abnormal differentiation, and disorganized mucosal architecture demonstrated higher TAG-72 expression than non-dysplastic epithelia. In contrast, normal gastric mucosa was generally non-reactive with MAb B72.3. Assays using serial sections of normal, benign and malignant gastric tissues with two MAbs (B1.1 and COL-6) directed against distinct epitopes of carcinoembryonic antigen (CEA) demonstrated differential reactivity, confirming that TAG-72 and CEA are distinct, non-coordinately expressed antigens. Our results suggest that TAG-72 antigen may be expressed in malignant and dysplastic epithelial cells, as well as in intestinalized epithelium of the stomach which has been closely related to subsequent carcinoma development. Hence, MAb B72.3 may be a useful immunohistochemical adjunct for detecting early foci of adenocarcinomas and premalignant lesions of the stomach.

Adenocarcinoma↗
PubMed1986

Expression of Leu-M1 antigens in carcinoma of the urinary bladder.

Anti-Leu-M1 antibody, which is well known to react with a human myelomonocytic antigen, was found to react with bladder carcinoma, but never with the normal bladder epithelium. Eighty-six cases of transitional cell carcinoma of the bladder were tested in sections of formalin-fixed and paraffin-embedded tissues by using an avidin-biotin immunoperoxidase technique. Fifty per cent of these cases were positive in Leu-M1, while the other three monoclonal antibodies (HBA4, HBG9 and HBH8), which were produced against a human bladder carcinoma cell line KU-1, reacted in 17 per cent, 27 per cent and 64 per cent of these cases respectively. Reactivities of these antibodies to 33 cases of normal bladder epithelium were Leu-M1, 0 per cent; HBA4, 0 per cent; HBG9, 0 per cent and HBH8, 30 per cent, respectively. Expression of Leu-M1 antigens in bladder epithelium seems to be specific for malignant change and highly frequent in the carcinoma patients. The relation between Leu-M1 expression and a degree or stage in bladder carcinomas, however, was not significant in our studies.

Animals↗
PubMed1985

Isoprenaline-like effects of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine on mechanical, biochemical and electrophysiological parameters in the mammalian heart.

The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca++ inward current (Isi) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and beta-adrenoceptor agonists exert their positive inotropic effects by increasing Isi via the common mediator cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Positive inotropic effect of Bay K 8644: cAMP-independence and lack of inhibitory effect of adenosine.

The aim of the present study was to characterize the positive inotropic effect of the Ca2+ channel activator Bay K 8644. In isolated guinea-pig papillary muscles we investigated whether adenosine and the R site adenosine receptor agonist (-)-N6-phenylisopropyladenosine (PIA) were able to antagonize the positive inotropic effect of Bay K 8644. The effect of Bay K 8644 and adenosine or PIA on myocardial cAMP content was also measured. The influence of adenosine and PIA on the positive inotropic effect of the beta-adrenoceptor agonist isoprenaline and of the phosphodiesterase inhibitor amrinone was studied for comparison. Adenosine and PIA antagonized the positive inotropic effects of isoprenaline and amrinone in a concentration-dependent manner. In contrast, adenosine or PIA did not affect the positive inotropic effect of Bay K 8644. The positive inotropic effect of Bay K 8644 was not accompanied by a change in the cAMP content of the papillary muscles. Additionally applied adenosine or PIA also failed to affect the cAMP content. It is concluded that an increased myocardial cAMP content is not involved in the positive inotropic effect of Bay K 8644. Moreover, the results support the view that adenosine and PIA only antagonize the positive inotropic effects of drugs known to increase myocardial cAMP content and that an increased myocardial cAMP content is a prerequisite for the manifestation of a negative inotropic effect of the nucleosides in ventricular cardiac muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Evidence for adenosine receptor-mediated isoprenaline-antagonistic effects of the adenosine analogs PIA and NECA on force of contraction in guinea-pig atrial and ventricular cardiac preparations.

The effects of the adenosine agonists (-)-N6-phenylisopropyladenosine (PIA) and 5'-N-ethylcarboxamideadenosine (NECA) on force of contraction, adenylate cyclase activity and normal as well as slow action potentials were studied in guinea-pig isolated atrial (left auricles) and ventricular preparations (papillary muscles). In auricles PIA and NECA exerted concentration-dependent negative inotropic effects with similar potencies (mean EC50:0.05 mumol l-1 for PIA and 0.03 mumol l-1 for NECA). Similar results were obtained in the presence of isoprenaline. In papillary muscles PIA and NECA alone had no effect on force of contraction but produced negative inotropic effects in the presence of isoprenaline (mean EC50:0.19 mumol l-1 for PIA and 0.10 mumol l-1 for NECA). In both preparations, the negative inotropic effects of PIA and NECA in the presence of isoprenaline were antagonized by the adenosine receptor antagonist 8-phenyltheophylline. In both preparations, PIA and NECA did not affect adenylate cyclase activity, both in the absence and presence of isoprenaline. In auricles the negative inotropic effects of both nucleosides were accompanied by a shortening of the action potential. This effect was also observed in the presence of isoprenaline. In papillary muscles the adenosine analogs did not detectably alter the shape of the normal action potential. Ca2+-dependent slow action potentials elicited in potassium-depolarized preparations also remained unaltered in the presence of PIA or NECA alone. However, the isoprenaline-induced enhancement of the maximal rate of depolarization of slow action potentials was attenuated by PIA or NECA.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1985

Carbohydrate chains on IgG2b: a requirement for efficient feedback immunosuppression.

The in vitro immunosuppressive ability of a monoclonal IgG2b-anti-trinitrophenyl antibody lacking carbohydrate chains (GORK-Tm) has been compared with the immunosuppressive ability of the intact antibody (GORK). The carbohydrate depletion of GORK-Tm was achieved by culturing the GORK hybridoma cells in media containing tunicamycin, an inhibitor of glycosylation. Both antibodies have been shown to have the same antigen and protein A-binding capacity, although GORK-Tm is deficient in complement fixation, antibody-dependent cellular cytotoxicity, binding to Fc receptors on macrophages, and rapid elimination of antigen-antibody complexes from the circulation. It is shown in these studies that although GORK antibodies are efficient immunosuppressors, suppressing up to 95% of the plaque-forming cell response, GORK-Tm antibody preparations with identical hemagglutinating and antigen-binding capacity are highly deficient in suppressing the immune response. These findings are of interest in two ways. First, it shows that the carbohydrate chains are of great importance for the immunosuppressive effects of IgG. Secondly, it also shows that the isotype IgG2b, in addition to all other murine isotypes, can efficiently suppress the humoral immune response.

Animals↗