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Biomedical subjects

B Ferry

Publications and source records attributed to B Ferry.

49 records · Page 3Linked to original sources

Impact of class II major histocompatibility complex antigen expression on the immunogenic potential of isolated rat vascular endothelial cells.

We have investigated the immunogenic potential of rat heart vascular endothelial cells by their ability to induce an accelerated rejection of a relevant heart allograft, and related the immunogenic potential to the expression of class II major histocompatibility complex (MHC) antigens on the endothelial cell surface. Only 12% of freshly isolated rat vascular endothelial cells express class II antigens in serum-free medium, and the level of expression is low as judged by immunoperoxidase staining and/or the ability of endothelial cells to bind staphylococci to the cell surface after treatment with monoclonal antibodies to the class II molecule. On the other hand, 99% of the endothelial cells under the same conditions express class I, and the level of expression is high. The class II antigen expression of vascular endothelial cells can be upregulated to more than 98% by recombinant gamma-interferon in vitro--and, concomitantly, the level of expression becomes high, even on the cell surface. Treatment with gamma-interferon did not substantially alter the level of class I expression. The endothelial cells expressing class II antigens weakly, are also weakly immunogenic in vivo: 10(7) endothelial cells are required to reduce the graft survival by 50% of that of the unprimed host. On the contrary, the endothelial cells of the same lineage induced to express class II antigens by gamma-interferon in vitro are highly immunogenic in vivo, as immunogenic as freshly-isolated spleen dendritic cells: only 10(4) endothelial cells are required to induce a 50% reduction of graft survival. These observations demonstrate for the first time that rat vascular endothelial cells are immunogenic in a primary transplantation response in vivo--and, moreover, that the immunogenic capacity of the endothelial cells is directly proportional to the extent of class II MHC antigen expression on the cell surface.

Animals↗

Frequency and functional characterization of specific T-helper cells infiltrating rat kidney allografts during acute rejection.

T-helper cells (ThC) play an important role in the induction of both cytotoxic T-cell responses and B-cell responses against the grafted organ. Furthermore, ThC alone are capable of causing graft rejection in T cell-deprived mice and rats. In view of these observations we found it important to analyse the frequency and functions of donor-specific ThC in the allograft and in the recipient lymphoid system during the course of acute renal allograft rejection. A limiting dilution assay was developed which, due to the absence of exogenous interleukin 2 (IL-2) and the low numbers of stimulator cells used, appears to be highly selective for the proliferation of specific ThC. Kidney transplants were performed from LBN (RT1n) to congenic Lewis (RT1l) strain differing in major histocompatibility complex (MHC) only. The inflammatory (white) cells were recovered from the graft, and blood and recipient spleen and the frequency of RT1n-responding ThC were determined at different times after transplantation. In the kidney graft itself, the frequency of ThC responding to RT1n MHC antigens was 1:3000 on day 2 and increased to 1:670-1320 at the peak of inflammation. In the spleen, the frequency increased from 1:1000 on day 0 to 1:200 on day 8, and remained high even after the graft was rejected. In the blood, the frequency stayed at the 1:400-1:800 level, and increased to 1:200 only after the graft had been completely destroyed. Individual ThC clones deriving from limited dilution assays of kidney and spleen cells were recovered and expanded with irradiated donor cells without IL-2 and finally with exogenous IL-2 only. All clones showed the T-helper (W3/25) phenotype, seven out of eight tested clones showed a specific anamnestic response to RT1n alloantigens and no response to RT1l or RT1a in a secondary MLC, 12 out of 12 clones produced IL-2 and 11 out of 11 clones produced gamma interferon upon re-stimulation with relevant allogeneic cells, and eight out of ten clones collaborated with syngeneic B cells for Ig synthesis, indicating that they were indeed derived from specific ThC and/or from their precursors. Taken together, the results demonstrate that specific ThC and/or their precursors represent only a very small minority in the graft-infiltrating inflammatory population. This makes it most unlikely that the ThC themselves are responsible for graft destruction; the results indicate rather that a major role of ThC in situ may be instruction of immunologically specific and nonspecific components of inflammation.

Animals↗

Antagonistic effects of gamma interferon and steroids on tissue antigenicity.

A single injection of 10(5) U/kg of recombinant rat IFN-gamma increases the amount of tissue dendritic cells up to sixfold, and concomitantly induces the (capillary) endothelial cells to express class II MHC antigens. Both responses peak on the third day after IFN-gamma injection, and the antigen expression returns to basic levels on day 7. Simultaneous administration of 1 mg/kg/d of methylprednisolone entirely abolishes both responses. These observations demonstrate, for the first time, that IFN-gamma and steroids have antagonistic effects on class II MHC antigen presentation in tissue, and suggest that one immunosuppressive mechanism of glucocorticosteroids in organ transplantation is downregulation of graft antigenicity.

Animals↗

Multiple epitopes on a human breast-carcinoma-associated antigen.

The monoclonal antibody (MAb) NCRC-11 identifies an epitope expressed variably in human breast cancer. The degree of expression of this epitope in primary operable tumours is closely related to the subsequent clinical course of the disease (Ellis et al., 1985). The target antigen for NCRC-11 was isolated from subcellular membranes of breast carcinomas and purified by immunoadsorbent chromatography. NCRC-11 epitopes were expressed upon a large glycoprotein of more than 400 kd. This material was susceptible to degradation by pronase and papain and contained N-acetylglucosamine, as indicated by its binding to wheat-germ agglutinin. The NCRC-11-defined antigen expressed epitopes for the anti-human milk-fat globule membrane antibodies HMFG-1 and HMFG-2, and other antibodies against epithelial membrane antigens (EMA, LICR-LON-M8). The reactivity of these antibodies with tumour membranes was also similar, but not identical, to that of the NCRC-11 antibody. In competitive binding-inhibition assays, these antibodies partially inhibited the binding of 125I-NCRC-11 antibody to antigen, suggesting that the epitopes involved are topographically closely associated. Sandwich immunoassays demonstrated that NCRC-11 epitopes are likely to represent repeated structures of the NCRC-11 antigen. The findings presented are interpreted as indicating that the NCRC-11 antigen expresses a variety of epitopes which are associated with normal differentiation and malignant change.

Animals↗

Immunocytochemical staining of breast carcinoma with the monoclonal antibody NCRC 11: a new prognostic indicator.

The staining of breast cancer with a new monoclonal antibody, NCRC 11, was studied in a series of 126 women with primary breast carcinoma. Tumour samples embedded in paraffin were tested, and the minimum duration of follow up was five years or to death. Altogether 119 tumours stained positively. There was a strong relation between the intensity of staining, divided on a four point scale, and patient survival. Patients whose tumours exhibited intense staining had an improved survival compared with those with less intensely staining tumours (p less than 0.0001). Staining related weakly to histological grade but not significantly to oestrogen receptor state or the pathological stage of lymph node disease. Mathematical analysis showed the relation to survival to be independent of the other known prognostic factors. Inclusion of intensity of staining with other factors in a prognostic index might permit a more accurate estimation of prognosis in patients with breast cancer.

Antibodies, Monoclonal↗

A monoclonal antibody, NCRC-11, raised to human breast carcinoma. 1. Production and immunohistological characterization.

The production of a mouse monoclonal IgM antibody, NCRC-11, raised against human breast carcinoma is described. It has been characterized immunohistologically. The antigen recognised has a wide but highly specific distribution in normal tissues, being virtually confined to the surface of certain epithelial cell types. It is found in some forms of epithelial metaplasia and most epithelial malignancies, particularly adenocarcinomas. The heterogeneity of staining in mammary carcinomas is outlined and is of particular interest. The immunohistological staining distribution of NCRC-11 is similar to other antibodies, including anti-epithelial membrane antigen, which were raised against human milk fat globule membrane. A competition experiment with some of these antibodies, using a flow cytofluorimeter, showed competition with one antibody, LICR LON/M8.

Antibodies, Monoclonal↗

High potency of the orally-active NMDA-receptor antagonist CGP 40 116 in inhibiting excitatory postsynaptic potentials of rat basolateral amygdala neurones in vitro.

Conventional intracellular recordings were used to monitor postsynaptic potentials of basolateral amygdala neurones (BLA) in brain slices comprising the BLA, the entorhinal cortex (EC) and the hippocampus, in which the EC-BLA connections were preserved. Stimulation of the BLA with a bipolar electrode elicited complex postsynaptic potentials consisting of alpha-amino-3-hydroxy-5-methyl-isoxazoleproprionic acid (AMPA) receptor-mediated fast excitatory postsynaptic potentials (fast EPSPs), gamma-amino-butyric acid [GABA(A)] receptor-mediated fast inhibitory postsynaptic potentials (fast IPSPs) and GABAB receptor-mediated slow IPSPs. Bath application of 10 microM of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and of 10 microM of the GABA(A) receptor antagonist bicuculline methiodide (BMI) revealed a N-methyl-D-aspartate (NMDA) receptor-mediated slow EPSPs, which was occasionally followed by a GABAB receptor-mediated slow IPSPs. Under these conditions, the log concentration-response curve for D-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 40 116), a newly developed drug with proposed NMDA-receptor antagonist properties, was compared to that obtained with the 'classic' antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) in inhibiting the NMDA-mediated postsynaptic potentials. CGP 40 116 (IC50: 130 nM) was over 30 times more potent than D-AP5 (IC50: 4100 nM) in reducing NMDA-mediated slow EPSP. In conclusion, the present study indicates that CGP 40 116, a new orally-active NMDA antagonist, shows a very high potency on NMDA receptors in the amygdala and may therefore be a valuable tool for studying the behavioural effect of NMDA-receptor mediated transmission in this structure.

2-Amino-5-phosphonovalerate↗

[Effects of frequency on muscular force induced by electric stimulation].

The aim of this work is to determine the effect of low frequency current (L) versus medium frequency current (M) in order to generate a different force level on soleus and gastrocnemius muscles. The experiment was conducted on 10 healthy, male volunteer subjects aged from 19 to 21 who provided informed consent to participate in the experiment. None of the subjects had experienced electrostimulation (ES) procedures before. The subjects were seated with vertical legs and horizontal thighs. Isometric force of the gastrocnemius and soleus muscles was measured using a strain gage dynamometer (100 daN). The transducer was adjusted on the knee, along the vertical axis of the leg. For the conditions of ES, a bi-phasic, symmetrical square wave signal was applied at each of five low frequencies: 20, 40, 60, 80 and 100 Hz and at each of six medium frequencies (2222 Hz) modulated or not, to yield 20, 40, 60, 80, 100 bursts of pulses. Maximum voluntary contraction (MVC) was also recorded. The phase duration was constant throughout 180 microseconds. The current level was set individually for each subject at the maximum that could be tolerated and applied during 10 s. Each contractile condition was randomly chosen. The forces produced by the different regimen of ES used are significantly different (P < 0.001). For each type of stimulation we got tetanic contractions. After an initial ramp, a nearly flat curve corresponding to tetanus was reached. For a 60 hz low frequency current, the force production reached 76% of MVC for a mean intensity of 58 mA, corresponding to a charge of 1253 microC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A cooperative program for the prevention of domestic accidents in children at the department of the Doubs. II. Educative aspects and evaluation].

Effective prevention of domestic accidents in children includes regimental and/or legislative action, information for parents and education of the children. The latter two strategies have been applied in the deparment of the Doubs in a cooperative health promotion program. Preschool and kindergarten structures were chosen and the pedagogical project involved acquainting the children with the idea of danger by use of a kit prepared by the "Comité Français d'Education pour la Santé" (French Committee for health education). This study was set up in two stages: "experimental" in 2 schools (1983-1984) and "operational" in 40 schools (1984-1985). In order to evaluate it, the population was divided into a control group and an experimental group. A total of 5,720 tests were carried out among 520 children. 494 parents and 82 teachers answered the questionnaires sent to them. The teachers were generally very positive about the effectiveness of education about dangers and the teaching activities which could be employed: discovery of environment, awareness of body, a.s.o. The changes in attitude were real and enduring among children. The parents changed their behavior significantly concerning the storing of poisonous products (medicines and household cleaning products), which allows to feel that this program can be effective in terms of risk reduction.

Accidents, Home↗