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Biomedical subjects

G Bal

Publications and source records attributed to G Bal.

6 recordsLinked to original sources

Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family.

Chemokines coordinate many aspects of leukocyte migration. As chemoattractants they play an important role in the innate and acquired immune response. There is good experimental evidence that N-terminal truncation by secreted or cell surface proteases is a way of modulating chemokine action. The localization of CD26/dipeptidyl peptidase IV on cell surfaces and in biological fluids, its primary specificity, and the type of naturally occurring truncated chemokines are consistent with such a function. We determined the steady-state catalytic parameters for a relevant selection of chemokines (CCL3b, CCL5, CCL11, CCL22, CXCL9, CXCL10, CXCL11, and CXCL12) previously reported to alter their chemotactic behavior due to CD26/dipeptidyl peptidase IV-catalyzed truncation. The results reveal a striking selectivity for stromal cell-derived factor-1alpha (CXCL12) and macrophage-derived chemokine (CCL22). The kinetic parameters support the hypothesis that CD26/dipeptidyl peptidase IV contributes to the degradation of certain chemokines in vivo. The data not only provide insight into the selectivity of the enzyme for specific chemokines, but they also contribute to the general understanding of CD26/dipeptidyl peptidase IV secondary substrate specificity.

Amino Acid Sequence↗

Truncation of macrophage-derived chemokine by CD26/ dipeptidyl-peptidase IV beyond its predicted cleavage site affects chemotactic activity and CC chemokine receptor 4 interaction.

The serine protease CD26/dipeptidyl-peptidase IV (CD26/DPP IV) and chemokines are known key players in immunological processes. Surprisingly, CD26/DPP IV not only removed the expected Gly1-Pro2 dipeptide from the NH2 terminus of macrophage-derived chemokine (MDC) but subsequently also the Tyr3-Gly4 dipeptide, generating MDC(5-69). This second cleavage after a Gly residue demonstrated that the substrate specificity of this protease is less restricted than anticipated. The unusual processing of MDC by CD26/DPP IV was confirmed on the synthetic peptides GPYGANMED (MDC(1-9)) and YGANMED (MDC(3-9)). Compared with intact MDC(1-69), CD26/DPP IV-processed MDC(5-69) had reduced chemotactic activity on lymphocytes and monocyte-derived dendritic cells, showed impaired mobilization of intracellular Ca2+ through CC chemokine receptor 4 (CCR4), and was unable to desensitize for MDC-induced Ca2+-responses in CCR4 transfectants. However, MDC(5-69) remained equally chemotactic as intact MDC(1-69) on monocytes. In contrast to the reduced binding to lymphocytes and CCR4 transfectants, MDC(5-69) retained its binding properties to monocytes and its anti-HIV-1 activity. Thus, NH2-terminal truncation of MDC by CD26/DPP IV has profound biological consequences and may be an important regulatory mechanism during the migration of Th2 lymphocytes and dendritic cells to germinal centers and to sites of inflammation.

Binding, Competitive↗

PC controlled toothbrush/dentifrice abrasion machine.

A toothbrush/dentifrice abrasion machine was developed to use in dental research laboratory. The mechanism was designed as a hexagonal block driven by two stepping motors which move the mechanism in four directions. In order to control the stepping motors speed, position and direction commands or signals were generated by a software written in C Programming Language and then these commands were applied the stepping motor drives through parallel port of a personal computer. The toothbrush/dentifrice abrasion machine was finally used to measure different longevity of tooth brush. It was experimentally shown that the mechanism can be used for highly accurate position and speed applications.

Dental Materials↗

Attenuation correction in SPECT using consistency conditions for the exponential ray transform.

Using data consistency conditions for the exponential ray transform, a method is derived to correct SPECT data for attenuation effects. No transmission measurements are required, and no operator-defined contours are needed. Furthermore, any 3D parallel-ray geometry can be considered for SPECT data acquisition, even unconventional geometries which do not lead to a set of 2D parallel-beam sinograms. The method is presented for both the 2D parallel-beam geometry and a particular 3D case, called the rotating slant hole geometry. Full details of the algorithms are given. Implementation has been carried out and results are presented in 2D and in 3D using simulated data.

Algorithms↗

The unique properties of dipeptidyl-peptidase IV (DPP IV / CD26) and the therapeutic potential of DPP IV inhibitors.

This review deals with the properties and functions of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5). This membrane anchored ecto-protease has been identified as the leukocyte antigen CD26. The following aspects of DPP IV/CD26 will be discussed : the structure of DPP IV and the new family of serine proteases to which it belongs, the substrate specificity, the distribution in the human body, specific DPP IV inhibitors and the role of CD26 in the intestinal and renal handling of proline containing peptides, in cell adhesion, in peptide metabolism, in the immune system and in HIV infection. Especially the latest developments in the search for new inhibitors will be reported as well as the discovery of new natural substrates for DPP IV such as the glucagon-like peptides and the chemokines. Finally the therapeutical perspectives for DPP IV inhibitors will be discussed.

Animals↗