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Biomedical subjects

A Hasse

Publications and source records attributed to A Hasse.

12 recordsLinked to original sources
PubMed1999

Preservation of Gi coupling of a chimeric EP3/I-type prostaglandin (IP) receptor.

For the EP3 subtype of prostaglandin E receptors, different C-terminal splice variants are known, which are coupled to distinct heterotrimeric GTP-binding proteins (G-proteins). To test the hypothesis that the C-terminal domain is essential for the G-protein-coupling specificity of the EP3 receptor, we exchanged the carboxyl-terminal tail of a porcine Gi-coupled EP3 receptor isoform for the corresponding C-terminal part of a Gs-coupled prostaglandin receptor. The porcine EP3 receptor was truncated at a lysine (K350) residue at the end of the seventh transmembrane region, representing the splicing site of the different EP3 receptor isoforms. The wild-type C-terminus (37 amino acids) was substituted by the C-terminal tail (89 amino acids) of the human I-type prostaglandin receptor (hIP-R). The G-protein coupling of the resulting chimeric receptor protein was studied in transfected Chinese hamster ovary (CHO) cells. Stimulation of the chimeric receptor protein with the EP3 receptor-specific agonist M&B 28.767 did not increase adenosine 3',5'-cyclic monophosphate (cAMP) formation but did reduce the forskolin-stimulated cAMP formation, indicating Gi coupling. Furthermore, the chimeric receptor did not show constitutive activity as demonstrated for the C-terminally truncated EP3 receptor. Thus, coupling specificity of the EP3 receptor is not exclusively mediated by the carboxyl-terminal tail, and constitutive activity of a C-terminally truncated EP3 receptor can be suppressed by the hIP-R C-terminus.

Amino Acid Sequence↗
PubMed1999

Versatility of vascularized fibula and soft tissue graft in the reconstruction of the mandibulofacial region.

The anatomical region "laterodorsal calf" with the fibula, the flexor muscles and the overlying skin served by the peroneal vessels, is a suitable donor region particularly for combined microsurgical transfer of bone and soft tissue. In a five and a half year period, 59 reconstructions, 39 (66%) with and 20 (34%) without soft tissue transfer, were performed. The versatility and the functional and esthetic results after osseous, osteocutaneous, osteomuscular and osteomyocutaneous tissue transfer are presented.

Adolescent↗
PubMed1998

Tolerance development to antimitogenic actions of prostacyclin but not of prostaglandin E1 in coronary artery smooth muscle cells.

This study compares the antimitogenic effects of iloprost and prostaglandin E1 on platelet-derived growth factor-BB stimulated DNA synthesis ([3H]thymidine incorporation) in bovine coronary artery smooth muscle cells. When added 20-24 h after stimulation with platelet-derived growth factor-BB (20 ng/ml), both iloprost and prostaglandin E1, concentration-dependently (IC50 3-5 nM) inhibited DNA synthesis. However, when added together with the growth factor (0-24 h), the inhibition of DNA synthesis by iloprost was markedly attenuated, indicating tolerance development. In contrast, no tolerance to antimitogenic effects of prostaglandin E1 or forskolin were observed. When added to iloprost-tolerant cells, both prostaglandin E1 and forskolin, still inhibited DNA synthesis. There was no evidence for transcriptional down-regulation of prostacyclin receptor gene by iloprost. The data demonstrate a tolerance development to antimitogenic actions of prostacyclin but not of prostaglandin E1 and suggest that the receptors, mediating the antiproliferative actions of these prostaglandins, may be different.

Alprostadil↗
PubMed1998

Antimitogenic effects of vasodilatory prostaglandins in coronary artery smooth muscle cells.

Vasodilatory prostaglandins (PGI2, PGE2, PGE1) are known inhibitors of proliferation of vascular smooth muscle cells (SMC) after stimulation with mitogenic factors. However, endogenous prostaglandins do not prevent SMC proliferation subsequent to vessel injury in vivo. Since vascular cells produce large amounts of antiproliferative prostaglandins, especially subsequent to COX-2 expression, insufficient vascular PGI2 formation is not likely to explain the failure of endogenous prostaglandins to prevent excessive SMC growth. In this paper we demonstrate a rapid development of tolerance to PGI2 in SMC, resulting in diminished antiproliferative activity. These findings may not only be relevant for the control of SMC growth by endogenously synthesized prostaglandins but also for clinical use of PGI2 mimetics.

Animals↗
PubMed1994

Enhancement of reporter gene de novo methylation by DNA fragments from the alpha-fetoprotein control region.

The 5'-upstream region of the rat alpha-fetoprotein (AFP) gene strongly increased de novo methylation of an adjacent chloramphenicol acetyltransferase (CAT) gene upon transfection into F9 mouse embryonal carcinoma cells. The same effect was exerted by a distal 775-base pair (bp) fragment and by 300- and 1-kb fragments preceding the transcriptional start site, but not by other parts of the control region. Further division of the larger, strongly active fragments resulted in a gradual decrease of methylation and clonal variation in the methylation patterns. The effect of the 775-bp fragment did not depend on its orientation. It was ablated by insertion of the mouse metallothionein I promoter between the AFP gene fragment and the CAT gene, but not by its insertion upstream of the AFP gene fragment. Two fragments from the AFP control region increasing methylation contained B1 and B2 small interspersed repetitive elements, respectively. B1 and B2 sequences of different origin also acted strongly to increase methylation. These findings support the idea that mammalian genes contain specific sequences involved in regulating their methylation. The effects of these sequences appear to be exerted in cis, to be dependent on proximity, but not on orientation, and to require an optimal size of 500-700 bp. Small retrotransposon sequences within such elements may be particularly effective in attracting de novo methylation.

Animals↗
PubMed1993

Highly efficient transactivation by the yeast Kluyveromyces lactis transcription factor LAC9 and its inhibition by the negative regulator GAL80 in mammalian cells.

Expression of the LAC9 gene from the yeast Kluyveromyces lactis in HepG2 human hepatoblastoma cells efficiently induced luciferase expression from reporter plasmids containing the four LAC9 binding sites from the K. lactis GAL1-GAL10 gene linked to a basal promoter. Induction was approximately 100fold and was dependent on the presence of the UAS sequence and an intact reading frame in the LAC9 gene. Additional cotransfection of constructs expressing the K. lactis GAL80 gene reduced luciferase activity by up to 98%. This inhibition was not affected by addition of 14mM galactose to the medium. No further yeast-specific factors appear necessary for efficient inhibition of LAC9 by GAL80, but additional gene products may be required for activation by galactose.

Animals↗
PubMed1992

De novo methylation of transfected CAT gene plasmid constructs in F9 mouse embryonal carcinoma cells.

To study the formation of DNA methylation patterns, plasmids containing promoters of different strengths in front of the bacterial chloramphenicol acetyltransferase reporter gene were transfected into F9 mouse embryonal carcinoma cells. Methylation of the integrated plasmids as well as copy numbers and activities of the reporter gene were determined for individual cell clones. The methylation pattern of the integrated plasmids was found to be determined by properties of the DNA sequence itself. In contrast, the specific methylation patterns were invariant with respect to integration site, copy number and arrangement of the integrates; methylation did also not correlate with transcriptional activity of the different promoters. Certain promoter regions may therefore contain signals recognized by the de novo methylation activity in embryonal carcinoma cells.

Animals↗
PubMed1979

Dental infection in a cirrhotic patient. Source of recurrent sepsis.

A patient with alcoholic cirrhosis had multiple episodes of sepsis with Klebsiella pneumonia. Repeated searches for the source of infection finally revealed the organism in the root of a tooth. Evidence indicated that this site was the primary source of infection. The importance of dental infections in alcoholics and the difficulty in diagnosing those infections are emphasized by this case.

Focal Infection, Dental↗