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Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 703 records · Page 39Linked to original sources
PubMed1987

Dissociation between onset of natural killer E-rosette forming cells and of T3-positive cells following HLA-mismatched T cell depleted bone marrow transplantation.

We have studied immunological reconstitution following partially HLA-incompatible T cell depleted bone marrow transplantation, compared with reconstitution following HLA identical T cell depleted and HLA identical untreated bone marrow transplantation. We often observed an early emergence of E-rosette forming cells that were T3 negative and displayed strong natural killer activity in the first group of patients. This activity was shown with fresh leucocytes as well as interleukin 2 grown cells. The appearance of T3+ cells was delayed in this situation compared to that observed in HLA identical bone marrow transplantation. The delay in T3+ cell differentiation and in cellular immune function development probably explains why NK rosette forming cells are early detected within 3-4 months following HLA mismatched bone marrow transplantation. This NK subset is likely to be present at an early stage in all types of bone marrow transplantation, but is most commonly observed simultaneously with the T3+ cells in HLA identical untreated bone marrow transplantation. The respective role of T cell depletion and HLA incompatibility in this phenomenon are discussed while patients' conditioning, cyclosporine A and graft-versus-host disease have been shown to be irrelevant for the dissociation between NK E-rosette forming cells and T3+ subset onsets.

Bone Marrow Transplantation↗
PubMed1987

[Bioequivalence of generic drugs and substitution: example of depot verapamil].

Following oral administration of 240 mg Verapamil-HCl as Isoptin RR, Veramex SR 240 and durasoptin SR 240, plasma concentration time curves of Verapamil and ECG changes were determined in 14 healthy subjects. There was a linear correlation between maximal plasma concentration and prolongation of PQ-intervals of the ECG. No hysteresis was observed when the changes in PQ-interval were plotted against plasma concentration. Comparison of concentration and effect profiles showed that the three formulations were not equivalent and a change in therapy from one to the other cannot be recommended.

Blood Pressure↗
PubMed1987

Assessment of symptoms of Parkinson's disease by apparative methods.

Established clinical scores assessing the severity of Parkinson's disease show high specificity but only low interrater reliability. Using them in therapy control in multicenter studies raises typical problems. We examined the MLS, a motor performance test, in an extended form including assessment of "tapping" regularity for its practicability in therapy control of Parkinson's disease. Assessing a group of right-handed healthy controls we obtained parameters which describe normal motor dexterity by mean values, standard deviations, age relationship and correlation between left and right hand. This method is thus a good tool for estimation of abnormalities in motor dexterity. In therapy control the comparison of results obtained before and after treatment allows a good objective evaluation of the therapeutic success.

Aged↗
PubMed1987

[Congenital heart defects. Frequency at autopsy].

Autopsies were performed on 3,071 stillborns and decreased children up to the age of 16 years at the Institute of Pathology of the Charité from 1969 to 1983. Congenital heart disease (CHD) was found in 814, i.e. 26.5% of the autopsies. Results of re-examination of 642 hearts with CHD are discussed. The most common malformations are ventricular septal defects, d-transpositions of the great vessels, tetralogy of Fallot and aortic coarctations. CHD was more frequently found in boys than in girls (1.5 : 1). The majority of the deaths occurred during the first year of life (78.8%). 20.1% of these took place during the perinatal period and 47.2% within the first 6 months of life. Additional cardiac anomalies were associated with the main defect in 81.8% of cases. The most common such associated defects were atrial and ventricular septal defects, aortic coarctations and other aortic arch anomalies. The frequency of extracardiac malformations in CHD was 7.2%. The most common anomalies were of the central nervous system, the gastrointestinal tract and the urinary system. Malformation syndromes were identified in 5.6% of the CHD cases, including Down's syndrome in 1.4%.

Adolescent↗
PubMed1986

Prevention of graft failure by an anti-HLFA-1 monoclonal antibody in HLA-mismatched bone-marrow transplantation.

Seven patients with immunodeficiencies (Wiskott-Aldrich syndrome, combined immunodeficiency, and osteopetrosis) were given a mouse monoclonal antibody against the alpha subunit of human leucocyte functional antigen (HLFA-1; CD18) to facilitate the engraftment of mismatched haploidentical related-donor bone marrow. Other conditioning included busulphan, cyclophosphamide, and antilymphocyte globulin. To prevent graft-versus-host disease the bone-marrow T cells were depleted with sheep erythrocyte rosetting and cyclosporin therapy was given. HLFA-1 antibody injections were well tolerated without side-effects except slight, transient fever (38-40 degrees) after the first injection. Engraftment was rapid in all seven patients. The regenerating leucocytes were of donor origin in all cases, and two patients have a mixed chimera. Two patients died from infections. The others are alive and well 60-395 days after transplantation. In a historical control group given the same treatment without anti-HLFA-1 infusion, only one of seven transplants partially engrafted; only two patients remain alive with autologous reconstitution but with uncorrected immunodeficiency.

Antibodies, Monoclonal↗
PubMed1986

Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985.

In this retrospective analysis of allogeneic bone-marrow transplantation (BMT) carried out between 1969 and 1985 at fourteen European centres in 162 patients with sixteen different types of inherited immunodeficiencies and osteopetrosis, the overall survival with functional grafts was 51.7% (85 patients), with a minimum follow-up of 5 months. In patients with severe combined immunodeficiency HLA-matched (n = 41) and T-cell-depleted HLA-mismatched BMT (n = 46) resulted in 68% and 57% disease-free survival, respectively; after HLA-mismatched transplants, older age (greater than 6 months) and adenosine-deaminase deficiency resulted in poorer survival. Eight other lethal immunodeficiencies, including profound T-cell deficiencies, Wiskott-Aldrich syndrome, Kostmann syndrome, LFA-1/CR 3/p150,95 deficiency, and Chediak-Higashi syndrome as well as malignant osteopetrosis, have been successfully treated by BMT. In this group, survival with functional graft was 47% with HLA-matched and 29% with T-cell-depleted HLA-mismatched BMT. Engraftment failure was the major complication in this group. Poorer prognosis was associated with older patients, profound T-cell deficiencies, and the degree of HLA incompatibility.

Adolescent↗
PubMed1986

Role of the LFA-1 molecule in cellular interactions required for antibody production in humans.

The lymphocyte function-associated antigen 1 (LFA-1) has been shown to play a role in various T cell functions in mice and humans including cytotoxicity, and proliferation to allogeneic cells and foreign antigens. These functions have been defined with specific monoclonal antibodies and were additionally confirmed by the investigation of patients with inherited deficiency in membrane LFA-1 expression. In this paper, we report our studies on the potential role of the LFA-1 molecule in T lymphocyte-dependent antibody responses. In a patient with a complete lack of membrane expression of LFA-1, there was no in vivo antibody response to vaccinal antigens such as tetanus, diphtheria toxoids, and polio virus, and no in vivo or in vitro antibody production to influenza virus, whereas serum immunoglobulin levels and antibodies to polysaccharides (isohemagglutinins, antibody to mannan, and a polysaccharide from Candida albicans) were detected in correlation with in vitro production of anti-mannan antibody. The defective antibody response to polypeptides was not secondary to poor antigen-specific T proliferation, because the latter was found to be present. Similarly, in vitro antibody production to influenza virus of normal cells was blocked by several anti LFA-1 monoclonal antibodies specific for the alpha subunit of the molecule, if they were added from the beginning of the culture. The antibody production blockade could be achieved with monoclonal antibody concentrations that partially preserved T cell proliferation. The helper effect of an influenza virus-specific helper T cell clone was also blocked. The targets of the blockade were shown by incubation experiments to be T cells and monocytes. In contrast, anti-LFA-1 monoclonal antibodies had no effect on pokeweed mitogen-induced B cell maturation into immunoglobulin-containing cells and on the anti-mannan antibody production. These combined data demonstrate that the LFA-1 molecule plays a role in T cell dependent antibody production to polypeptidic antigens but not in the antibody response to polysaccharides, although the antibody response to mannan is T cell dependent. It is proposed that the LFA-1 molecule is required to some extent for a antigen-presenting cells-T lymphocyte interaction and for the maintenance of a close association between antigen-specific helper T cells and small resting B lymphocytes. Polysaccharidic antigens that exhibit repetitive antigenic determinants might cross-link membrane immunoglobulins on B lymphocytes, thus allowing B cells to pass through a first step of activation requiring cognate T-B cell interaction.

Antibodies, Monoclonal↗
PubMed1986

Self-tolerance to host and donor following HLA-mismatched bone marrow transplantation.

The transplantation of T cell-depleted HLA-haploidentical bone marrow can correct the severe combined immunodeficiency disease (SCID) caused by the inherited absence of T lymphocytes. Despite a different environment, no severe graft-vs.-host reaction occurred and engrafted T lymphocytes became functional. We have studied tolerance of engrafted T lymphocytes to donor and host HLA antigens in four SCID patients who have been transplanted with bone marrow from one of their HLA-haploidentical parents. Graft-vs.-host reaction was prevented by T cell depletion of infused bone marrow using E rosetting and by in vivo administration of cyclosporine A. Subsequent to bone marrow transplantation (BMT), the engrafted T lymphocytes were shown to be unresponsive in vitro towards host cells collected prior to BMT. Generally, this tolerance could not be explained by a suppressive mechanism. Nevertheless, in one patient suppressive cells were found transiently. In contrast to the early appearance of a tolerance towards host, a reactivity of engrafted donor cells towards donor was always observed within the first 300 days post-grafting. This autoreactivity was mediated by T cells of donor origin and its targets were HLA class II molecules (at least HLA-DR and DQ). The progressive disappearance of this autoreactivity was correlated with the engraftment of Ia-positive cells (monocytes plus B lymphocytes) of donor origin and the achievement of complete immunological reconstitution. In the patient showing the strongest autoreactivity, a donor-specific T cell line has been grown which was shown to specifically inhibit the proliferative response of donor lymphocytes. Concomittantly, the immunological reconstitution remains poor in this patient. These data suggest that tolerance to HLA class II molecules is dependent on the presence of the relevant HLA class II molecule-expressing cells allowing the elimination or the suppression of T lymphocytes specifically directed at these molecules.

Bone Marrow Transplantation↗
PubMed1986

Defective membrane expression of the LFA-1 complex may be secondary to the absence of the beta chain in a child with recurrent bacterial infection.

Membrane and intracellular processing of the LFA-1 macromolecular complex, known to be involved in cytolytic function of T lymphocytes, was investigated in a child with recurrent bacterial infections, impaired natural killer activity, T cell-mediated lymphocytolysis and absent adhesion and migration of phagocytic cells. Monoclonal antibodies to the LFA-1 alpha and beta subunits, able to precipitate the LFA-1 alpha, 180-kDa chain, the p151 chain and beta 94-kDa chain (shared by both alpha chains), were used in immunoprecipitation studies of patient and control phytohemagglutinin-blasts. Neither of the alpha chains nor the beta chain were found in precipitates obtained from 125I-surface-labeled patient cells in contrast to controls. However, the precursor of the LFA-1 alpha chain, a 170-kDa polypeptide, was identified in lysates of biosynthetically labeled patients' cells. These results suggest that the defective membrane expression of the LFA-1 complex may be secondary to the absence of the mature beta chain.

Antigens, Surface↗
PubMed1986

Possible T4-HLA class II interaction as an essential event in antigen-specific helper T lymphocyte-dependent B cell activation.

We have previously shown that the interaction between influenza virus-specific helper T lymphocytes and B lymphocytes is HLA class II restricted (Fischer, A. et al., Eur. J. Immunol. 1985. 15: 620). In the present study, we used a panel of antibodies specific for the T4 and HLA-DR molecules to investigate the role of both structures in T-B lymphocyte interaction. Several anti-T4 monoclonal antibodies were shown to block the in vitro antibody production to A/Bangkok influenza virus while they were unable to inhibit the A/Bangkok-induced proliferation of specific helper T cell clones. Some anti-HLA-DR monoclonal antibodies inhibited the antibody production to A/Bangkok, the target of the inhibition being either monocytes or B lymphocytes. The incubation of helper T cell clones with an infra-inhibitory concentration of anti-T4 antibody and of B lymphocytes with an infra-inhibitory concentration of anti-HLA-DR antibody resulted in a mutual enhancement of inhibition. Such synergistic interactions were not observed using combinations of anti-T4 and anti-B membrane structures such as p35 or LFA-1 or anti-HLA-DR and anti-T membrane structures such as T11 or LFA-1. First, these results indicate that the T4 molecule plays an essential role in T-B cell interaction even when it is not absolutely required for T cell proliferation. Second, they strongly suggest that the T4 molecule directly interacts with HLA-DR at the B cell surface. Whether such interaction is required to enhance the stability of T3/T cell receptor-antigen plus HLA class II association or whether T4-HLA-DR may transduce a signal towards B lymphocytes that is required in B cell activation remains unknown.

Antibodies, Monoclonal↗