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Biomedical subjects

U Griesser

Publications and source records attributed to U Griesser.

3 recordsLinked to original sources

Substance P and vasoactive intestinal polypeptide in the streptozotocin-induced diabetic rat retina.

PURPOSE: Little knowledge exists about how neurotransmitters behave in the diabetic retina. In this study, the authors measured the concentration of two neuropeptides, substance P and vasoactive intestinal polypeptide, in the streptozotocin-induced diabetic rat retina in a time-dependent manner. METHODS: The retinas of 1-, 3-, 5-, 8-, and 12-week diabetic rats were processed using a highly sensitive radioimmunoassay for both substance P and vasoactive intestinal polypeptide. Furthermore, the peptide-immunoreactivities were characterized by high-pressure liquid chromatography. RESULTS: Substance P and vasoactive intestinal polypeptide were found to be significantly reduced with a maximum decrease of 28.6% (+/-6.7) and 64.5% (+/-10.7) after 5 weeks, respectively. The peptide-immunoreactivities were found in a major peak coeluting with the synthetic peptides indicating that the quantitative values measured by radioimmunoassay represent the authentic peptides. CONCLUSIONS: The reduction of substance P and vasoactive intestinal polypeptide is in clear contrast to the amino acid transmitters GABA and glycine, which have been shown to be elevated in this early stage of diabetic retinopathy. This finding is important for three reasons: First, the decrease may result in reduced excitability of inner retinal neurons, as both peptides are known to modulate the excitability of these neurons; second, the decrease may be the consequence of a depressing and/or damaging effect by excitotoxins; and third, it may help explain why neovascularizations do not occur in this animal model, although VEGF is massively upregulated, as substance P is a very potent vascular growth factor.

Animals↗

LST1: a gene with extensive alternative splicing and immunomodulatory function.

The gene of the leukocyte-specific transcript (LST1) is encoded within the TNF region of the human MHC. The LST1 gene is constitutively expressed in leukocytes and dendritic cells, and it is characterized by extensive alternative splicing. We identified 7 different LST1 splice variants in PBMC; thus, 14 LST1 splice variants (LST1/A-LST1/N) have been detected in various cell types. These isoforms code for transmembrane as well as soluble LST1 proteins characterized by two alternative open reading frames at their 3' end. We demonstrate the presence of the transmembrane variant LST1/C on the cell surface of the monocytic cell lines U937 and THP1. Recombinant expression of LST1/C permitted its profound inhibitory effect on lymphocyte proliferation to be observed. In contrast, the alternative transmembrane variant LST1/A, the extracellular domain of which shows no amino acid sequence homology to LST1/C exerted a weaker but similar inhibitory effect on PBMC. These data demonstrate the protein expression of LST1 on the cell surface of mononuclear cells, and they show an inhibitory effect on lymphocyte proliferation of two LST1 proteins although they have only a very short amino acid homology.

Adjuvants, Immunologic↗

Expression and regulation of the thrombopoietin receptor variants MPLP and MPLK in PBMC.

The human c-mpl proto-oncogene encodes the receptor for thrombopoietin (TPO), which plays a central role in magakaryopoiesis and platelet production. Recent results showed that c-mpl mRNA expression is restricted to CD34(+) cells, megakaryocytes, and platelets. The authors analysed mRNA expression by reverse transcription and PCR (RT-PCR) of the transmembrane Mpl variants, MPLK and MPLP, in magakaryocytic cell lines, peripheral blood mononuclear cells (PBMC), lymphocytes, and monocytes. Transcription of both Mpl variants was detected in freshly isolated PBMC and the megakaryocytic cell line, DAMI, whereas none could be detected in the megakaryocytic cell line Meg-01. The cytokines TPO, interleukin 11 (IL-11), erythropoietin (EPO), and stem cell factor (SCF), which are known stimulators of megakaryopoiesis, but not interleukin3 (IL-3), increased MPLP mRNA detection in PBMC during 96 h of incubation. However, concomitantly the detection of MPLK transcripts decreased in these cells. MPLP was also detected in monocytes, B-lympocyte and T cell populations. In contrast, MPLK mRNA expression was low in monocytes, B and T cells, and no clear increase in transcription detection was observed during stimulation of these cells.

B-Lymphocytes↗