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Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 613 records · Page 34Linked to original sources
PubMed1990

Immunohistochemistry of the guinea-pig trachea using an anti-idiotypic antibody recognizing substance P receptors.

The airways receive a dense innervation from sensory neurons containing substance P (SP). An anti-SP anti-idiotypic antibody (anti-Id ab) recognizing SP receptors was previously characterized pharmacologically and proved to be useful in immunohistochemistry of the central nervous system. This antibody was used to localize SP binding sites in the guinea-pig trachea by immunohistochemistry. Immunolabelling was considered as specific when it could be prevented by a) preabsorption of the anti-Id ab with a C-terminal specific monoclonal anti-SP antibody, and b) preincubation of the tissue sections with either of the tachykinins, substance P and neurokinin A, in the presence of the inhibitor of neutral endopeptidase, phosphoramidon, and addition of these compounds into the antibody incubation medium. Moreover, immunofluorescence was absent when the acetone-fixed of fresh frozen sections were exposed to the detergent Tween 20 prior to immunohistochemistry, which points to a membrane localization of the detected tissue antigen, as expected for SP receptors. Compared with previous reports on autoradiographic localization of SP receptors in the guinea-pig trachea, the present immunohistochemical approach proved to be superior in enabling discrimination of labelled elements: Trachealis muscle, cylindrical epithelial cells and some roundish, singly lying cells in the epithelium and subepithelial lamina propria displayed specific immunofluorescence. These morphological findings match well with the known pharmacological actions of SP on the guinea-pig trachea.

Animals↗
PubMed1990

Differentiation of embryonic chick sympathetic neurons in vivo: ultrastructure, and quantitative determinations of catecholamines and somatostatin.

The ultrastructural and transmitter development of lumbar sympathetic ganglia was studied in embryonic day-6 through -18 chick embryos. At embryonic day 6, ganglia are populated by two morphologically distinct types of neuronal cells and Schwann cell precursors. The neuronal populations basically comprise a granule-containing cell and a developing principal neuron. Granule-containing cells have an irregularly shaped or oval nucleus with small clumps of chromatin attached to the inner nuclear membrane and numerous large (up to 300 nm) membrane-limited granules. Developing principal neurons display a more rounded vesicular nucleus with evenly distributed chromatin, prominent nucleoli, more developed areas of Golgi complexes, and rough endoplasmic reticulum and large dense-core vesicles up to 120 nm in diameter. There are granule-containing cells with fewer and smaller granules which still display the nucleus typical for granule-containing cells. These granule-containing cells may develop toward developing principal neurons or the resting state of granule-containing cells found in older ganglia. Both granule-containing cells and developing principal neurons proliferate and can undergo degeneration. At embryonic day 9 there are far more developing principal neurons than granule-containing cells. Most granule-containing cells have very few granules. Mitotic figures and signs of cell degeneration are still apparent. Synapse-like terminals are found on both developing principal neurons and granule-containing cells. Ganglionic development from embryonic day 11 through 18 comprises extensive maturation of developing principal neurons and a numerical decline of granule-containing cells. Some granule-containing cells with very few and small granules still persist at embryonic day 18. The mean catecholamine content per neuron increases from 0.044 femtomol at embryonic day 7 to 0.22 femtomol at embryonic day 15. Concomitantly, there is a more than 6-fold increase in tyrosine hydroxylase activity. Adrenaline has a 14% share in total catecholamines at embryonic day 15. Somatostatin levels are relatively high at embryonic day 7 (1.82 attomol per neuron) and are 10-fold reduced by embryonic day 15. Our results suggest the presence of two morphologically distinct sympathetic neuronal precursors at embryonic day 6: one with a binary choice to become a principal neuron or to die, the other one, a granule-containing cell, which alternatively may develop into a principal neuron, acquire a resting state or die.

Animals↗
PubMed1990

Overlapping palindromic sequences associated with somatic deletion and meiotic recombination of MHC class I genes.

H-2L-null variants were immunoselected from a transfected murine fibroblast cell line carrying a single copy H-2L gene, and were characterized to determine the basis for the loss of this MHC class I cell surface product. Molecular analysis indicated that inactivation of H-2L expression in nearly every null clone resulted from an apparent deletion or rearrangement of 5'-flanking and 5'-coding H-2L sequences, with breakpoints consistently mapping to within a 550 bp GC-rich region between exon 1 and the middle of intron 2. Notably, this region of the H-2L gene contains a large number of overlapping, inverted repeat sequences as well as potential topoisomerase I cleavage sites. Examination of several in vivo mutant class I genes, believed to have been generated by recombination, has revealed that each of these genes bears similar palindromic structures overlapping or adjacent to the regions of sequence exchange. These findings suggest that inverted repeat sequences may play a role in recombination and deletion within the MHC class I multigene family.

Animals↗
PubMed1990

Prospective study of the occurrence of monoclonal gammapathies following bone marrow transplantation in young children.

We have prospectively studied the occurrence of monoclonal serum immunoglobulins in 38 recipients of BMT. Patients were young children with primary immunodeficiencies (n = 31), other inherited diseases (n = 4), leukemia (n = 2), or aplastic anemia (n = 1). Twenty-nine received an HLA-nonidentical marrow and nine an HLA-identical marrow. Serum monoclonal immunoglobulins were detected by the immunofixation method. Monoclonal immunoglobulins were found in 26 patients. Monoclonal components were more frequently detected in patients with primary severe T cell deficiencies (21/25) rather than in the other patients (6/13). In 7 of 29 recipients of HLA-nonidentical transplants, versus 0 out of 9 recipients of HLA-identical transplants, serum monoclonal immunoglobulins were found associated with a B lymphocyte proliferation syndrome due to an Epstein-Barr virus infection. In this group, monoclonal immunoglobulins were detected early, prior to the onset of the clinical syndrome. The simultaneous occurrence of several monoclonal immunoglobulins was more frequent in these patients, while monoclonal immunoglobulin concentrations increased faster, especially those of IgM isotype. These characteristics may allow in patients at risk (recipients with primary T cell immunodeficiencies and receiving HLA-nonidentical transplantation) an earlier diagnosis of B lymphocyte proliferative syndrome that may eventually lead to early and more efficient therapy.

Bone Marrow Transplantation↗
PubMed1990

Specific elimination of alloreactive T cells by an anti-interleukin-2 receptor B chain-specific immunotoxin.

Graft-versus-host disease and graft rejection remain the two principal causes of morbidity and mortality after major-histocompatibility-complex-mismatched bone marrow transplantation. Human and animal models suggest that both CD4+ and CD8+ T cell subsets present in the donor inoculum are responsible for their initiation. Since the human mixed lymphocyte culture (MLC) and the HLA-restricted cytotoxicity may reflect cellular interactions occurring during GVHD and graft rejection, inhibitions of these responses may represent useful approaches for screening functional T cell depletion in experimental bone marrow transplantation studies. For this purpose, we have tested the possibility of removing the host-specific allogeneic T cells present in the marrow. After a two-day MLC, the specifically activated host alloreactive blood or bone marrow T cells were incubated with the ricin A-chain toxin conjugated with the antibody 33B3.1 directed against the human receptor of interleukin 2 (33B3.1-IT). A complete inhibition of a primary MLC and of cytotoxic activities was observed as well as a disappearance of IL-2R(+) (p55) T cells. This method had limited consequence upon the alloreactivity of blood or marrow T cells toward a third unrelated party. The limiting-dilution analysis of residual alloantigen-reactive T lymphocytes has shown that this depletion results in a twentyfold to fiftyfold reduction of antihost reactivity. The procedure was also shown not to inhibit the growth of marrow precursors for granulocytes and macrophages.

Hematopoietic Stem Cells↗
PubMed1990

Cytokine control of peripheral-blood CD23 expression and sCD23 release: differential regulation by IL-2 and IL-4.

CD23 expression on peripheral-blood lymphocytes (PBL) was studied under the influence of cytokines. It is shown that IL-2 induced CD23 expression on human peripheral-blood B cells. Evidence is presented that the IL-2 induced CD23 expression and release of soluble CD23 (sCD23) are not mediated by IL-4. In comparison to IL-4, the IL-2-induced CD23 expression and sCD23 release revealed kinetic differences and were not inhibited by anti-IL-4. The prestimulation of PBL with Staphylococcus aureus strains Cowan 1 (SAC) led to a pronounced reduction in basal CD23 expression and to a change in the response of cytokines. Subsequent stimulation with IL-4 induced CD23 to the same extent as on unstimulated cells, whereas the IL-2-induced CD23 expression and sCD23 release were greatly reduced. Interferon gamma showed no effects on the IL-4-stimulated CD23 expression of SAC-PBL, whereas the IL-2-induced CD23 expression was suppressed. Furthermore, we demonstrate that the stimulation with IL-2/IL-4 inhibits the effects of the individual cytokine; this inhibition is also seen for immunoglobulin (E, G, M) synthesis.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1990

Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy.

Pearson's marrow-pancreas syndrome (McKusick No. 26056) is a fatal disorder of hitherto unknown etiology involving the hematopoietic system, exocrine pancreas, liver, and kidneys. The observation of high lactate/pyruvate molar ratios in plasma and abnormal oxidative phosphorylation in lymphocytes led us to postulate that Pearson's syndrome belongs to the group of mitochondrial cytopathies. Since rearrangements of the mitochondrial genome between direct DNA repeats were consistently found in all tissues tested, our results show that this disease is in fact a multisystem mitochondrial disorder, as suggested by the clinical course of the patients. Based on these observations, we would suggest giving consideration to the hypothesis of a defect of oxidative phosphorylation in elucidating the origin of other syndromes, especially those associated with an abnormal oxidoreduction status in plasma.

Anemia, Sideroblastic↗
PubMed1990

Growth rate of incidental meningiomas.

A meningioma was incidentally identified with computerized tomography (CT) in 17 patients without relevant clinical signs. The tumor was not removed, but biopsy confirming a meningioma was obtained from one patient. Tumor growth rate was calculated from repeat CT scans or follow-up magnetic resonance imaging. The annual growth rate ranged from less than 1% to 21%. It is concluded that in nonsymptomatic meningiomas with a low growth rate a nonsurgical approach may be warranted.

Aged↗
PubMed1990

Germ-line mosaicism simulates genetic heterogeneity in Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome (IMD2) is an X-linked recessive immunodeficiency. Initial linkage studies mapped the disease locus on the proximal short arm of the X chromosome, a localization which was further refined to the interval framed by DXS7 and DXS14. We have recently shown that a novel hypervariable locus, DXS255, is very closely linked to the disease gene and is likely to be, at present, the marker closest to the disease gene. The analysis of one family, however, displayed conflicting linkage results, as all of the informative markers situated in the Xp11-q22 region appeared to recombine with the disease locus in two "phase-known" meioses. We have shown by X-inactivation studies that the segregation of the disease through three obligate carrier females in this family originates from a grandpaternal mosaicism, which accounts for the apparent recombinations. This shows that germ-line mosaicism can simulate genetic heterogeneity in linkage studies.

Blotting, Southern↗
PubMed1990

Regulation of CD23 expression, soluble CD23 release and immunoglobulin synthesis of peripheral blood lymphocytes by glucocorticoids.

Evidence was obtained that glucocorticoids are capable of modulating the CD23 expression and soluble(s) CD23 release of peripheral blood lymphocytes (PBL). We demonstrate that interleukin-2 (IL-2)- and IL-4-induced CD23 expression are susceptible to glucocorticoids to a different degree. Prednisolone suppressed the spontaneous and IL-2-induced CD23 expression on PBL of healthy donors. The IL-4-induced CD23 expression was influenced much less by prednisolone, but the expression kinetics was altered. The modulation of the expression kinetics appears to be due to a priming effect of prednisolone. Differences were also apparent when the susceptibility of PBL from healthy and atopic donors towards the effect of prednisolone on the IL-4-induced CD23 expression was studied. Preactivation of PBL with Staphylococcus aureus strain Cowan I abolished the differences. Prednisolone also suppressed the sCD23 release from unstimulated and IL-2- or IL-4-stimulated PBL and enhanced the immunoglobulin (E,G,A,M) synthesis of PBL. This enhancement appears to be due to a priming effect, since pre-stimulation of PBL with prednisolone was sufficient to enhance the immunoglobulin synthesis. The IL-4-induced IgE synthesis of PBL with or without spontaneous in vitro IgE synthesis was synergistically enhanced by glucocorticoids.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1990

[Allogenic bone marrow graft in thalassemia major. The French experience].

From August 1985 to April 1988, 17 patients have been allografted in France for TM. Fourteen (82%) are alive, 10 (58%) are cured and 4 in autologous reconstitution. Three died, 2 of whom after a second transplantation, and 2 due to CMV interstitial pneumonia. Ten of 17 were conditioned by cyclophosphamide (Cy: 200 mg/kg) and busulfan (Bu: 14 mg/kg): 10 are alive, 6 cured and 4 in autologous reconstitution. Five received Cy (200 mg/kg) Bu (16 mg/kg) +/- total lymphoid irradiation (TLI) (3 patients): 2 patients are cured (one after hepatic veno-occlusive disease), and 3 died. For 2 patients, conditioning included total body irradiation: both are cured. Graft versus host (GVH) reaction prevention included: 4 T cell depletion (with additional prevention in 3; 2 are cured, one is in autologous reconstitution, 1 died); 5 cyclosporine alone (2 cured, 2 autologous reconstitution, 1 dead) and 8 cyclosporine + methotrexate (6 cured, 1 autologous reconstitution, 1 dead). Four of 12 evaluable patients presented a less than or equal to 2 grade acute GVHd. None had received a T cell depleted marrow. Bone marrow transplantation is the only curative treatment currently available for TM patients with HLA identical donors. It should be proposed to any young patient before iron overload is established. Optimal conditioning includes Cy (200 mg/kg) + Bu (14 mg/kg). The best protocol for GVHd prevention remains to be defined.

Adolescent↗
PubMed1990

T cell adhesion.

Antigen recognition by the T cell receptor cannot ensure by its own T cell activation. Other membranes molecules are required in order to achieve transient but strong adhesion of the T cell to the antigen presenting cell. Two main molecular adhesion pathways have been characterized involving the CD2 molecule binding the LFA-3 molecule and the LFA-1 molecule binding the ICAM-1 or ICAM-2 molecule. These results have been provided by the use of the three approaches, i-e inhibition of T cell activation and adhesion by monoclonal antibodies, the study of the adhesion of lymphocytes that do not express one or several adhesion molecules and finally the demonstration that the transfection of gene(s) coding for adhesion molecules into fibroblasts cotransfected with HLA molecules make the latter cells able to present antigen(s). The importance of the concept of antigen-independent T cell adhesion has been further underlined by in vivo use of monoclonal antibodies specific for adhesion molecule(s): LFA-1. Such antibody can efficiently block rejection of HLA non identical bone marrow in children. This opens further prospect of immunosuppression through blocking of T cell adhesion.

Antibodies↗
PubMed1990

[The diagnostic value of bronchoalveolar lavage in opportunistic pneumonia following kidney transplantation].

In 18 renal transplant patients with pneumonia under ciclosporin therapy the diagnostic value of BAL and of covered micro brush smears were compared. In 10 out of 18 cases partly atypical bacterial pathogens were cultivated and cytomegaly was diagnosed 4 times, mycosis twice, whereas 2 cases could not be clarified. A granulocytosis in the differential cell pattern correlated with a bacterial infection.

Bronchoalveolar Lavage Fluid↗
PubMed1990

[Hypogammaglobulinemia G and A with hypergammaglobulinemia M. Apropos of 12 cases].

Hyper IgM with low IgG and IgA is a rare humoral immunodeficiency. We presently report 12 new observations which have been clinically and immunologically studied. On one occasion the syndrome was found to be associated with congenital rubella. Since 10/12 children were male, X-linked inheritance is suggested which has been confirmed in 2 cases. In most cases (9/12), the first infections occurred within the first year of life. The syndrome is causing upper and lower respiratory tract infections due to bacteria, as well as gut infections. Lymphoid organ hyperplasia has been noted in 11/12 patients. Polyclonal hyper IgM serum contrasts with low or absent IgG, IgA and IgE. In some instances, some IgM antibody response was detected. A dysfunction of cellular immunity was not detected. Autoimmunity was detected in 3 patients. Finally, transient neutropenia occurred in 50% of the patients. Intravenous immunoglobulin G substitution treatment resulted in a significant reduction in the occurrence of infections as well as in normalization of growth rate. Immunoglobulin infusion also frequently induced correction of hyper IgM and neutropenia.

Antibody Formation↗
PubMed1989

Close linkage of hypervariable marker DXS255 to disease locus of Wiskott-Aldrich syndrome.

Linkage analyses in 5 families with Wiskott-Aldrich syndrome show that a novel hypervariable locus, DXS255, is very closely linked to the disease gene on the proximal short arm of the X chromosome. DXS255, with a maximum lod score of 5.42 at theta = 0.00 (90% confidence interval 0.00, 0.10) and heterozygosity of over 90%, is likely to be the closest available marker to the Wiskott-Aldrich gene and to be helpful in genetic counselling of affected families.

Chromosome Mapping↗
PubMed1989

Development of immunologic functions after bone marrow transplantation in 33 patients with severe combined immunodeficiency.

We retrospectively analyzed the development of lymphocytes and of the main immunological functions in 33 patients with severe combined immunodeficiency who survived at least 6 months after bone marrow transplantation (BMT). Eighteen patients received HLA-identical BM and 15 received HLA-nonidentical BM. Development of immune functions occurred faster after HLA-identical BMT as full T- and B-lymphocyte-mediated responses were present at day 186 versus 505, respectively (P = .05). In addition, antibody responses remain completely or partially absent in 8 of 15 patients of the second group. Detection of antibody response after HLA-incompatible BMT correlated with engraftment of donor B cells in informative cases. In patients who received an HLA-nonidentical BMT after chemotherapy (6 of 15), development of immune functions occurred more rapidly and 6 of 6 had B-cell functions, including normal antibody production. Autoimmunity was not uncommon and was found after HLA-incompatible BMT (4 of 15) or after HLA-partially phenotypically identical BMT (2 of 3). Antibodies were in most cases specific for blood cells. Occurrence of autoimmunity correlates with poor B-cell functions and to a lesser extent with defective T-cell responses. This type of study may lead to definition of a more accurate strategy for performing BMT in patients with severe combined immunodeficiency.

Adolescent↗