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Biomedical subjects

G Grütz

Publications and source records attributed to G Grütz.

7 recordsLinked to original sources
PubMed2005

The expression of legumain, an asparaginyl endopeptidase that controls antigen processing, is reduced in endotoxin-tolerant monocytes.

The exposition of monocytes to lipopolysaccharide (LPS) primarily causes a massive inflammatory response that is then followed by a hyporesponsive state of these cells. This latter state is called endotoxin tolerance and is characterized by (i) the attenuated production of proinflammatory mediators after repeated LPS treatment, and (ii) the diminished antigen presentation and T-cell stimulation capacity. The data presented here indicate that LPS priming causes a specific decrease in the expression of legumain (the asparaginyl endopeptidase responsible for the key step in antigen processing) in monocytes. In these cells, the fraction of major histocompatibility complex (MHC) class II loaded with CLIP was increased. In contrast to monocytes, LPS priming provoked an increase of legumain expression in B cells. Reduced monocytic expression of legumain was also found in critically ill patients supporting the suitability of endotoxin tolerance as an experimental model of clinical postinflammatory immunodeficiency.

Antigen Presentation↗
PubMed1995

Introduction of the octanucleotide restriction site SwaI into the bicistronic vector pTiSDT for high level synthesis of proteins.

The octanucleotide recognition site for the endonuclease SwaI was introduced into the Escherichia coli bicistronic expression vector pTiSDT by mutating a single position in the coupling SD sequence between a truncated form of the cro-gene and the multicloning site. This mutation does not influence the expression rate. The introduction of this restriction site allows high level production of proteins, that are modified only by an N-terminal methionine incorporated as the start codon.

Base Sequence↗
PubMed1995

Tumorigenic activity of the BCR-ABL oncogenes is mediated by BCL2.

BCR-ABL is a chimeric oncogene generated by translocation of sequences from the c-abl protein-tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, p210BCR-ABL and p190BCR-ABL, are produced that are characteristic of chronic myelogenous leukemia and acute lymphoblastic leukemia, respectively. Their role in the etiology of human leukemia remains to be defined. Transformed murine hematopoietic cells can be used as a model of BCR-ABL function since these cells can be made growth factor independent and tumorigenic by the action of the BCR-ABL oncogene. We show that the BCR-ABL oncogenes prevent apoptotic death in these cells by inducing a Bcl-2 expression pathway. Furthermore, BCR-ABL-expressing cells revert to factor dependence and nontumorigenicity after Bcl-2 expression is suppressed. These results help to explain the ability of BCR-ABL oncogenes to synergize with c-myc in cell transformation.

Animals↗
PubMed1994

Identification and characterization of a TNF alpha antagonist derived from a monoclonal antibody.

Peptides derived from the CDRs of the anti-TNF alpha monoclonal antibody Di62 were tested for inhibition of binding of Di62 to TNF alpha as well as of TNF alpha to its 55 and 75 kDa receptor. A peptide derived from the CDR1 of the light chain was shown to specifically inhibit Di62 binding to TNF alpha with markedly higher activity (Ki = 4 microM) than all other CDR-derived peptides. This peptide also significantly inhibited binding of TNF alpha to its 55 and 75 kDa receptor and protected L929 cells from the cytotoxic effect of TNF alpha (IC50 = 6 microM). The C-terminal region of this peptide, which is homologous to the 55 and 75 kDa TNF receptor, was found to be essential for activity.

Amino Acid Sequence↗
PubMed1994

VH/VL gene expression in polyreactive-antibody-producing human hybridomas from the fetal B cell repertoire.

Among a panel of nearly 3,000 IgM-producing hybridomas obtained from 22 independent fusions of human fetal lymphocytes (liver/spleen; 15th-36th gestational week) a high number (5-10%) produced autoantibodies, independently of the gestational age. A significant portion of these autoantibodies was found to be polyreactive, i.e. capable of binding to more than two antigens, when tested against a set of five antigens of the internal (ssDNA, thrombocytes, keratin) and external (lipid A, tetanus toxoid) environment. Analyzing the IgVH genes utilized in eight polyreactive and two putatively nonpolyreactive hybridomas, members of the VHI, III, IV and VI families were found once, seven times, once and once, respectively, mostly with germline identity. All but one of the utilized gene elements could be related to the biased VH gene repertoire said to be expressed during the early ontogeny of the human immune system. We also noted a bias for the utilization of DN1 (3/10), DHQ52 (3/10), JH2 (4/10) and JH6 (4/10) elements, whereas all heavy-chain CDR3 regions manifest a diversity by addition of N nucleotides and/or exonuclease activity on coding segments. In addition, VL segments which belong to different subgroups of both isotypes were found to be used. The molecular basis of polyreactive immunoglobulin specificities in human fetuses is discussed.

Antibodies, Bispecific↗
PubMed1993

Detection of inhibition of HIV-1 protease activity by an enzyme-linked immunosorbent assay (ELISA).

An ELISA is described for the detection of HIV-1 protease activity using an immobilized gag-related polyprotein as substrate. Proteolytic activity was demonstrated with either bacterial lysates expressing HIV-1 protease or purified protease. No cleavage was observed with a protein preparation from control bacteria not expressing HIV-1 protease. Under these conditions the aspartyl-type protease inhibitor, pepstatin A, was found to inhibit HIV-1 protease cleavage by > 90% at a concentration of 0.1 mM. This assay may be a useful tool for the study of both synthetic and natural inhibitors of HIV-1 protease.

Enzyme-Linked Immunosorbent Assay↗