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Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 595 records · Page 33Linked to original sources
PubMed1991

Preparative-scale enzyme-catalyzed peptide synthesis using solubilizing N-terminal protecting groups.

Several amino acid derivatives with the negatively charged N alpha-protecting groups Maleyl (Mal) and Citraconyl (Cit) were synthesized and used in enzyme-catalyzed peptide synthesis. Compared to commonly used alpha-amino protecting groups in chemical peptide synthesis (Z, Fmoc, Boc, etc.), these charged protecting groups strongly increase both water solubility of different aromatic amino acid derivatives and activities of synthesis reactions. As a consequence of the solubilizing effect, we used these groups in the kinetically controlled peptide synthesis choosing kyotorphin (tyrosyl-arginine) as a model peptide. With Mal-Tyr-OEt as substrate and Arg-OEt as nucleophile, we succeeded in the alpha-chymotrypsin-catalyzed production of about 12 kg of Tyr-Arg (50.4% overall yield) in a 300 l batch experiment.

Dipeptides↗
PubMed1991

Detection of mannose-binding proteins on mouse lymphocytes.

D-Mannose influences both the allogeneic stimulation of mouse spleen cells and the induction of cytotoxic T-lymphocytes. At low concentrations (10(-3) -4 x 10(-3) M), D-mannose increases [3H]thymidine incorporation and induction of cytotoxic cells. Higher concentrations lead to an inhibition of the allogeneic response. To test the involvement of mannose receptors, unstimulated and allogeneically stimulated spleen cells were lysed and the proteins electrophoretically separated. After blotting, the D-mannose-binding structures were identified by means of a biotinylated mannose-neoglycoprotein and avidin peroxidase. Two mannose-binding proteins of unstimulated mouse spleen lymphocytes with a molecular mass of 29 and 31 kDa were detected. In vitro allogeneically stimulated spleen lymphocytes show three other mannose-binding proteins with a molecular mass of 53, 65, and 76 kDa.

Animals↗
PubMed1991

[Symptomatology and diagnosis of Borna encephalitis of horses. A case analysis of the last 13 years].

In a retrospective study of 38 horses with Borna encephalitis which were clinically and histopathologically examined in the "I. Medizinische Tierklinik" in Munich between 1977 and 1990, the epidemiology, the clinical symptomatic and the diagnostic procedures available are presented. Indirect immunofluorescence showed antibodies in the serum of 12 out of 29 cases (41%) and in the cerebrospinal fluid (CSF) of 17 out of 28 cases (61%). The evaluation of 23 cases in which indirect immunofluorescence of serum and CSF, and also the post mortem virological and histopathological examination of the brain were performed, showed that a diagnosis was made in 61% of the cases before death. In 39% the diagnosis of Borna disease could only be reached post mortem.

Animals↗
PubMed1990

Human severe combined immunodeficiency disease: phenotypic and functional characteristics of peripheral B lymphocytes.

Human severe combined immunodeficiency disease (SCID) includes an X-chromosome-linked type characterized by a complete absence of mature T cells, hypogammaglobulinemia but normal or elevated number of B cells, suggesting that the disease results from a block in early T cell differentiation. It has been shown that B cells from obligate carrier women of this disorder exhibit the preferential use of the nonmutant X chromosome as the active X (as shown for T cells), suggesting that the SCID gene product has a direct effect on B cells as well as on T cells. To examine this question, we analyzed the phenotypic and functional characteristics of peripheral B cells from nine infants with SCID. We found a constant absence of spontaneously expressed activation Ag on B cell membrane from all SCID patients tested which contrasts with the phenotypic pattern exhibited by age-matched infants whom all cells bearing surface Ig express the 4F2 Ag and to a lesser extent the transferrin receptor. Concurrently, B cells from SCID patients have a profound impairment in their responses to stimuli that induce in vitro B cell proliferation and differentiation. Although rIL-2 and low-Mr B cell growth factor are potent inducers of proliferation on age-matched infants' B cells, they are poorly efficient in inducing proliferation of anti-mu-activated SCID B cells. This impairment is not related to the resting B cell phenotype of SCID B cells as shown by comparison with normal resting B cells. Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation. These results suggest that the SCID gene defect has a direct effect on B cells and is required during B cell maturation.

Antigens, CD↗
PubMed1990

European experience of bone-marrow transplantation for severe combined immunodeficiency.

The outcome of bone-marrow transplantations (BMT) carried out between 1968 and March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was analysed. Recipients of HLA-identical BMTs (70) had a 76% probability of survival (median follow-up 73 months). Of the 32 treated since 1983, 97% have been cured (median follow-up 41 months). This good prognosis was associated with rapid development of T and B cell function. HLA-non-identical, T-cell-depleted, BMT (n = 100) gave significantly lower survival (52%; median follow-up 47 months). Factors associated with poor prognosis were the presence of a lung infection before BMT, absence of a protected environment, and use of female donors for male recipients. Use of a conditioning regimen significantly increased the frequency of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in more frequent engraftment of donor B lymphocytes and myeloid cells. Donor B-cell chimerism was strongly associated with the development of normal B-cell function.

Actuarial Analysis↗
PubMed1990

[Renal and neurological toxicity of acyclovir. Apropos of a case].

The occurrence of anuria and stupor in a patient treated with acyclovir afforded the opportunity to discuss the renal and neurological toxicity of this drug. Acute renal insufficiency by crystallization of acyclovir and intratubular obstruction is a not infrequent side effect. The risk depends on the dose, the administration mode, the patient's state of hydration and preexisting renal failure. The evolution is typified by a rapid onset (after 24-48 h) and a prompt recovery after ending the treatment. The demonstration in urinalysis of crystals within leukocytes helps to establish the diagnosis. Neurological involvement can vary from confusion to coma. The cerebrospinal fluid is normal and the electroencephalogram shows diffuse slowing. A favorable outcome after ending treatment is the rule. Awareness of the risk factors associated with renal and neurological toxicity should lead to a reduction of its frequency.

Acute Kidney Injury↗
PubMed1990

Inositol 1,4,5-trisphosphate- and arachidonic acid-induced calcium mobilization in T and B lymphocytes.

Inositol triphosphate (IP3) formation and increase in intracytoplasmic calcium are mediators of signal transduction in lymphocytes. It has been proposed that IP3 induces Ca2+ release from intracellular stores. It is in order to study the relationship between these two events that we have analyzed the effect of IP3 addition on Ca2+ mobilization in permeabilized resting T and B lymphocytes, EBV-B lymphocytes, and HTLV1-T lymphocytes. IP3 induces a rapid and significant release of Ca2+ from the endoplasmic reticulum in a dose-dependent manner. Ca2+ release is more sensitive to IP3 addition in cycling cells (EBV-B lymphocytes and HTLV1-T lymphocytes) than in resting T and B lymphocytes. Arachidonic acid (AA) induces Ca2+ release from the endoplasmic reticulum (ER) in a manner similar to that of IP3. Neither component has an effect on Ca2+ accumulated in mitochondria, and they have no additive effects suggesting that they act on a similar Ca2+ pool. These results directly demonstrate that in T and B human lymphocytes IP3 mobilizes Ca2+ from ER as in other cellular systems and that other potential second messengers, namely AA, could play a significant role in the internal mobilization of calcium during T and B lymphocyte activation.

Adenosine Triphosphate↗
PubMed1990

Phenotypic and functional characteristics of human newborns' B lymphocytes.

It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e., 4F2 and IL-2R, both associated in significant proportions with CD23 and Bac-1. These membrane Ag were found both on CD5(+) and CD5(-) B cells. Newborns' B cells do not exhibit other activation markers because they express surface IgD, and because their size, RNA, and DNA contents do not differ from those of adults' B cells, indicating that they are in the G0/G1 cell cycle phase. Newborns' B cell proliferation can be induced by rIL-2, rIL-4, low m.w. B cell growth factor, and by Staphylococcus aureus protein A. It is presently difficult to build a hypothesis accounting for all the specific findings made on newborns' B cells. It is not known for instance whether CD5(+) and (-) B cells belong to distinct subsets as suggested by the fluorescence intensity curve obtained with an anti-CD5 antibody or to distinct stages in a unique pattern of B cell maturation during fetal and newborn life. This may indicate that partially activated B cells actually produce natural polyspecific autoantibodies of the IgM isotype found in newborns' human serum.

Antigens, CD↗
PubMed1990

Regulation of T helper-B lymphocyte adhesion through CD4-HLA class II interaction.

Antigen-independent adhesion of CD4+ T lymphocytes to Epstein-Barr virus (EBV)-transformed B cells is mediated by CD2/lymphocyte function-associated antigen (LFA)-3 and LFA-1/intracellular adhesion molecule (ICAM)-1. Although some anti-CD4 antibodies block the antigen-independent adhesion of CD4+ T lymphocytes, the CD4-HLA class II interaction does not appear to significantly contribute to the forces of cell adhesion since CD4+ T cells equally bind HLA class II+ and HLA class II- mutant B cells. In addition, conjugates formed between CD4+ T cells and HLA class II- B cells remain stable for at least 1 h while CD4+T/HLA class II+ B cell conjugate percentages promptly drop off. Down-regulation of CD4 or spontaneous low expression of CD4 also results in a persistance of conjugates formed with B cells. The role of the CD4-HLA class II interaction has been further studied by investigating the inhibitory effect of synthetic 12-mer peptides analogous to HLA class II and containing the Arg-Phe-Asp-Ser sequence conserved in the beta 1 domain. These peptides were previously found to inhibit HLA class II-restricted T cell responses, this sequence being thought to be involved in CD4-HLA class II interaction. These peptides block conjugate formation of CD4+ resting T cells or clones but not of CD8+ T cells, by interacting with the T cells as shown by preincubation experiments. Down-regulation of CD4 or spontaneous low expression results in the loss of the inhibitory activity. The peptide-mediated inhibition is neutralized by a soluble dimeric CD4 molecule. Alteration within the Arg-Phe-Asp-Ser sequence results in a significant loss of inhibition. It is thus proposed that the CD4-HLA class II interaction negatively regulates antigen-independent adhesion of T cells, this interaction involving the highly conserved Arg-Phe-Asp-Ser sequence in the HLA class II beta 1 sequence as a CD4-binding site.

Amino Acid Sequence↗