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M Ditto

Publications and source records attributed to M Ditto.

6 recordsLinked to original sources

Contamination of Austrian soil with caesium-137.

Austria ranks among the countries that have been most strongly affected by the Chernobyl fallout. The mean contamination with 137Cs is 21.0 kBq/m2, of which 18.7 kBq/m2 is due to the Chernobyl accident, whereas global fallout contributes 2.3 kBq/m2. Maximum values of total 137Cs contamination are nearly 200 kBq/m2. Total deposition of Chernobyl 137Cs on Austrian territory is 1.6 PBq or a fraction of around 2% of the 137Cs released from the reactor. 2115 measurements were used to draw the Austrian "caesium map". The geographical pattern of fallout distribution shows regional differences of contamination as high as 1:100.

Austria↗

Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage.

CD26 is a leukocyte activation marker that possesses dipeptidyl peptidase IV activity but whose natural substrates and immunological functions have not been clearly defined. Several chemo-kines, including RANTES (regulated on activation, normal T cell expressed and secreted), have now been shown to be substrates for recombinant soluble human CD26. The truncated RANTES(3-68) lacked the ability of native RANTES(1-68) to increase the cytosolic calcium concentration in human monocytes, but still induced this response in macrophages activated with macrophage colony-stimulating factor. Analysis of chemokine receptor messenger RNAs and patterns of desensitization of chemokine responses showed that the differential activity of the truncated molecule results from an altered receptor specificity. RANTES(3-68) showed a reduced activity, relative to that of RANTES(1-68), with cells expressing the recombinant CCR1 chemokine receptor, but retained the ability to stimulate CCR5 receptors and to inhibit the cytopathic effects of HIV-1. Our results indicate that CD26-mediated processing together with cell activation-induced changes in receptor expression provides an integrated mechanism for differential cell recruitment and for the regulation of target cell specificity of RANTES, and possibly other chemokines.

Calcium↗

Regulation of anti-HIV-1 activity of RANTES by heparan sulfate proteoglycans.

The role of cell surface proteoglycans in CC chemokine-mediated anti-HIV-1 activity in T cells and macrophages was investigated. Enzyme digestion of heparan sulfate (HS), but not chondroitin sulfate, from the surface of PM1(CD26H) cells (a human T cell line selected for high CD26 expression) rendered them resistant to the antiviral effects of RANTES and macrophage-inflammatory protein-1beta at otherwise inhibitory chemokine concentrations. HIV-1 infection of macrophages, however, was inhibited only partially, even at high concentrations of RANTES, and this inhibition was not prevented by HS removal. Flow cytometry revealed that digestion of cell surface proteoglycans, including HS, prevented the binding of RANTES at 10 to 100 nM concentrations to PM1(CD26H) cells. However, the binding of RANTES to activated macrophages occurred only at higher concentrations (100-300 nM) and was mostly chondroitin sulfate, and not HS, dependent. These results support a role for HS in facilitating the interaction of CC chemokines with the cell surface and the consequent inhibition of HIV-1 infection. The absence of HS-dependent binding of RANTES at lower concentrations to macrophages is consistent with the resistance of these cells to the antiviral effects of chemokines.

Cell Line↗

CD26 expression correlates with entry, replication and cytopathicity of monocytotropic HIV-1 strains in a T-cell line.

Experiments to identify cell determinants involved in HIV-1 tropism revealed a specific decrease in the expression of the T-cell activation antigen CD26 after monocytotropic (M-tropic) but not T-cell line-tropic (T-tropic) virus infection of the PM1 T-cell line. The level of CD26 expression in single-cell clones of PM1 correlated with the entry rate and cytopathicity of M-tropic HIV-1 variants, resulting in preferential survival of cells with low CD26 levels after infection. Experiments with recombinant viruses showed that the third hypervariable region of the envelope gp120 plays an important role in this selection process. This study identifies CD26 as a key marker for M-tropic human immunodeficiency virus type 1 (HIV-1) infection and suggests a mechanism for the early loss of CD26-expressing cells in HIV-1-infected individuals.

Amino Acid Sequence↗

Antitermination of early transcription in phage HK022. Absence of a phage-encoded antitermination factor.

In phage lambda and its relatives most early phage genes are located downstream from transcription termination sites, and full gene expression requires suppression of termination (or antitermination). Phage HK022, a lambda relative, also antiterminates early transcription, but, unlike its relatives, does so in the absence of any active phage gene product. We found no functional equivalent of the lambda N antitermination protein in HK022. In addition, nus mutations, which alter host proteins required for lambda antitermination, have no apparent effect on HK022 early gene expression. We have shown that terminators located several thousand base-pairs from the start point of transcription are suppressed, and that in the left operon suppression requires a short, promoter-proximal segment. A 40 bp region within this segment is repeated in the right operon. The chromosomal locations of these repeated segments resemble those of the nut antitermination sites of other lambdoid phages, but the HK022 sites lack the conserved sequence elements of the nut sites. It appears that HK022 antiterminates early transcription in a novel way.

Bacteriophage lambda↗