PubMed Health⌕ Search

Biomedical subjects

R Förster

Publications and source records attributed to R Förster.

At least 37 records · Page 2Linked to original sources
PubMed1999

The murine chemokine receptor CXCR4 is tightly regulated during T cell development and activation.

We have characterized the murine homolog of the HIV-co-receptor CXCR4 during T cell development and activation. Our data demonstrate that this chemokine receptor, although highly conserved between human and mouse, is differently expressed and regulated in both species. Mitogenic activation resulted in an increase of surface CXCR4 on murine T cells within 2 days, whereas the receptor was strongly down-regulated on human T cells during this period. Furthermore, intraperitoneal immunization of mice resulted in a strong increase of splenic and mesenteric cytotoxic T cells co-expressing CXCR4. It is interesting that, on thymocytes, expression of CXCR4 is restricted to CD4+CD8+ cells. Stromal cell-derived factor-1alpha, a natural ligand of CXCR4, induced chemotaxis of thymocytes and was found to counteract dexamethasone-induced apoptosis to a certain extent in these cells. Thus, our data show that expression of CXCR4 is tightly controlled on murine T cells and indicate that this highly conserved chemokine receptor might serve different functions in humans and mice.

Animals↗
PubMed1999

Frequency data for the STR loci HumFibra (FGA) and HumACTBP2 (SE33) in a population of Germans and Turks from South-West Germany.

Population studies were carried out on German and Turkish individuals from South-West Germany using the short tandem repeat (STR) systems HumFibra (n = 138 Turkish and 1161 German individuals) and HumACTBP2 (n = 202 Turkish and 1338 German individuals). After electrophoresis 19 alleles could be identified for HumFibra and 55 for HumACTBP2. No significant deviations from Hardy-Weinberg equilibrium were observed.

Alleles↗
PubMed1999

[Ultrasonography guided versus anatomically oriented puncture of the internal jugular vein for central venous catheterization].

AIM: Ultrasonography guided puncture (UGP) of the internal jugular vein (IJV) carried out by an expert is considered to be superior to the anatomically orientated puncture (AOP). Whether routine use of the UGP lowered the number of unsuccessful punctures and complications was unknown. Both puncture techniques were compared in a random study. METHOD: Between 10/93 and 3/94, 77 patients who needed central venous catheterisation for thorax or cardiac surgery were included in the study. 84 (42 vs 42) punctures were performed by seven anesthetists, all of whom had a great deal of experience with AOP, using either one or the other technique. The UGP was demonstrated and assisted once by an expert. A conventional ultrasound unit with a 7.5 MHz transducer was used. The number of unsuccessful first punctures, overall rate of unsuccessful punctures, morbidity and puncture time were compared. RESULTS: The unsuccessful first punctures using UGP occurred significantly less frequently (7 vs 19, p < 0.005). Fewer unsuccessful punctures were evidenced (9 vs 73, p < 0.001). One arterial puncture occurred with each of the puncture techniques. Five hematomas were observed in patients where AOP was used. Four of these patients were adipous and at least six unsuccessful punctures had already been carried out. The punctures lasted comparatively the same length of time (UGP: 59 s vs AOP: 60 s, p > 0.05). CONCLUSION: UGP is superior to AOP of the IJV also in routine use. It should be used more frequently in elective situations.

Cardiac Surgical Procedures↗
PubMed1999

[Thoracoscopy versus thoracotomy. The dilemma of the comparison and its meaning for quality assurance in thoracic surgery].

The need for scientific investigation into the benefits of thoracoscopy in comparison to thoracotomy as well as State intervention to assure quality in the field of surgery motivated the members of the commission of endoscopic surgery of the German Society of Thoracic Surgery to conduct a pilot project at their hospitals. This pilot project was expected to analyse data on the outcome and a selection of variables concerning trauma and postoperative quality of life of some 400 patients treated between 8/95 and 10/95 at 5 thoracic surgical clinics. On completion of the pilot project the course of 141 patients undergoing different thoracic operations at 4 thoracic surgery departments had been documented to various degrees. 60 patients for various indications received a thoracoscopy, 72 a thoracotomy. In 9 patients thoracoscopy was converted to thoracotomy (6.4%). Eight of the 141 patients died in the postoperative course (5.7%), overall morbidity was 15.6%. There was a slight but statistically not significant difference concerning mortality and morbidity in favor of thoracoscopy (1.7 vs. 9.7% and 10 vs. 19.4%). But, there was a selection of malignant diseases, higher age and high risk patients towards thoracotomy. In subgroups of patients undergoing operations not bigger than the resection of three lung wedges only time of operation and length of incision revealed to be significantly shorter for thoracoscopy (69(25-190) min vs. 128(24-240)min, p = 0.0013; 6(4-8)cm vs. 23(12-35)cm, p = 0.0001). Borderline significance was reached by the Spitzer-Index in advantage for thoracoscopy (8(2-10)points vs. 7(0-10)points, p = 0.0728). Thoracotomy and thoracoscopy are access procedures used with different indications in different patients. Differences concerning trauma and quality of life if present are marginal and will need studies to be outlined. Quality assurance in thoracic surgery using a standardized documentation will not succeed under the given circumstances.

Adult↗
PubMed1998

Downstream activation of a TATA-less promoter by Oct-2, Bob1, and NF-kappaB directs expression of the homing receptor BLR1 to mature B cells.

The chemokine receptor, BLR1, is a major regulator of the microenvironmental homing of B cells in lymphoid organs. In vitro studies identify three essential elements of the TATA-less blr1 core promoter that confer cell type- and differentiation-specific expression in the B cells of both humans and mice, a functional promoter region (-36 with respect to the transcription start site), a NF-kappaB motif (+44), and a noncanonical octamer motif (+157). The importance of these sites was confirmed by in vivo studies in gene-targeted mice deficient of either Oct-2, Bob1, or both NF-kappaB subunits p50 and p52. In all of these animals, the expression of BLR1 was reduced or absent. In mice deficient only of p52/NF-kappaB, BLR1 expression was unaffected. Thus our data demonstrate that BLR1 is a target gene for Oct-2, Bob1, and members of the NF-kappaB/Rel family and provides a link to the impaired B cell functions in mice deficient for these factors.

Animals↗
PubMed1998

MAGE-11 protein is highly conserved in higher organisms and located predominantly in the nucleus.

The MAGE-11 gene belongs to a family whose products were identified first in tumor tissue. The MAGE-11 gene product has not been characterized in detail. We have isolated MAGE-11 cDNA from HeLa cells and confirmed the presence of MAGE-11 protein and of at least 2 other MAGE proteins (MAGE-1 and MAGE-3) in this cell line. Monoclonal antibodies (MAbs), obtained by using a GST-MAGE-11 fusion protein, detect MAGE-11 protein in HeLa cells as a 48 kDa protein. In contrast to other known proteins of the MAGE family, MAGE-11 is found mainly in the nucleus. Immunoprecipitation out of whole-cell extracts from different species reveals that MAGE-11 protein is highly conserved among mammalian cells, suggesting a conserved and important function.

Animals↗
PubMed1998

CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells.

CD40 ligand (CD40L, CD154), a transmembrane protein structurally related to the cytokine TNF-alpha, was originally identified on stimulated CD4+ T cells, and later on stimulated mast cells and basophils. Interaction of CD40L on T cells with CD40 on B cells is of paramount importance for the development and function of the humoral immune system. CD40 is not only constitutively present on B cells, but it is also found on monocytes, macrophages and endothelial cells, suggesting that CD40L has a broader function in vivo. We now report that platelets express CD40L within seconds of activation in vitro and in the process of thrombus formation in vivo. Like TNF-alpha and interleukin-1, CD40L on platelets induces endothelial cells to secrete chemokines and to express adhesion molecules, thereby generating signals for the recruitment and extravasation of leukocytes at the site of injury. Our results indicate that platelets are not only involved in haemostasis but that they also directly initiate an inflammatory response of the vessel wall.

Blood Platelets↗
PubMed1998

Intracellular and surface expression of the HIV-1 coreceptor CXCR4/fusin on various leukocyte subsets: rapid internalization and recycling upon activation.

We describe the expression and regulation of the HIV-1 coreceptor CXCR4/fusin. Using anti-CXCR4 mAb, we demonstrate that this chemokine receptor is highly expressed on neutrophils, monocytes, B cells, and naive T cells among peripheral blood cells. In secondary lymphoid organs CXCR4 was found to be expressed on B cells. However, individual variations with regard to surface expression could be observed on T cells. Expression of the receptor is not confined to the cell surface, as large amounts of intracellular stores can be found on various leukocytes. Upon activation with phorbol esters the amount of cell surface-expressed CXCR4 on lymphocytes increases twofold within 30 s before it is completely down-regulated within the next 2 min. Incubation of leukocytes with stroma derived factor-1alpha, the natural ligand for CXCR4, induces down-regulation of up to 60% of surface-expressed receptors in a pertussis toxin-insensitive manner. Interestingly, receptor cross-linking caused by incubation of cells with anti-CXCR4 mAb triggers receptor trafficking, in that the receptor is rapidly internalized and recycled to the cell surface. Therefore, receptor internalization and recycling may regulate the functional interaction of the receptor with envelope proteins during an initial step of HIV-1 infection.

3T3 Cells↗
PubMed1997

Abnormal expression of the B-cell homing chemokine receptor BLR1 during the progression of acquired immunodeficiency syndrome.

The putative chemokine receptor BLR1 has been identified as the first G-protein-coupled receptor involved in B-cell migration and in microenvironmental homing to B-cell follicles and to germinal centers. In healthy individuals, expression of BLR1 is restricted to all mature recirculating B cells and to a subpopulation of T-helper memory cells. In the present study, we analyzed the distribution of BLR1 on defined lymphocyte subsets during the progression of acquired immunodeficiency syndrome. It is shown that the proportion of T-helper memory cells coexpressing BLR1 continuously decreases during the infection, whereas a high proportion of gamma/delta T cells expressing BLR1 can be found in peripheral blood. The latter subpopulation is restricted to lymphoid tissues in healthy individuals. Most interestingly, in 75% of all human immunodeficiency virus (HIV)+ individuals, peripheral blood B cells were identified as not expressing BLR1 and phenotypically resembling germinal center cells of lymphoid tissue. Using BLR1 as a marker molecule, this study identifies peripheral blood lymphocytes in HIV+ individuals that are usually restricted to lymphoid tissue in healthy individuals. Because HIV infection is active in lymphoid tissue even at the clinically latent stage, aberrant expression of the B-cell homing chemokine receptor BLR1 might be an early indicator for the onset of destruction of lymphoid tissue.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Analyzing cytotoxic T lymphocyte activity: a simple and reliable flow cytometry-based assay.

A flow cytometry-based assay for analyzing cytotoxic T lymphocyte (CTL) activity is presented. This new approach is characterized by easy handling, the generation of highly reproducible data sets and is not dependent on the use of radioactivity. Before exposure to primed CTL effector cells the target cells were labeled with the green fluorescent dye DiO18(3) which is incorporated stably into the cell membrane. After a 4-h incubation period, samples were counterstained with the red fluorescent nuclear dye propidium iodide in order to permit discrimination between live and dead cells within both cell populations. The assay has been used to quantitate CTL effector activity against allogeneic lymphoblasts. Results derived from this novel flow cytometry assay show an excellent correlation (r = 0.988) with data obtained using the standard 51chromium release assay. An additional advantage of the assay is that freshly prepared splenocytes may be used as target cells because culturing and activation of target cells is no longer required. The results demonstrate that the fluorescent dyes DiO18(3) and propidium iodide in combination with flow cytometry permit accurate analysis of cytotoxic T cell activity.

Animals↗
PubMed1997

Identification of pirin, a novel highly conserved nuclear protein.

In this article we describe the molecular cloning of Pirin, a novel highly conserved 32-kDa protein consisting of 290 amino acids. Pirin was isolated by a yeast two-hybrid screen as an interactor of nuclear factor I/CCAAT box transcription factor (NFI/CTF1), which is known to stimulate adenovirus DNA replication and RNA polymerase II-driven transcription. Pirin mRNA is expressed weakly in all human tissues tested. About 15% of all Pirin cDNAs contain a short 34-base pair insertion in their 5'-untranslated regions, indicative of alternative splicing processes. Multiple Pirin transcripts are expressed in skeletal muscle and heart. Western blots and immunoprecipitations employing monoclonal anti-Pirin antibodies reveal that Pirin is a nuclear protein. Moreover, confocal immunofluorescence experiments demonstrate a predominant localization of Pirin within dot-like subnuclear structures. Homology searches using the BLAST algorithm indicate the existence of Pirin homologues in mouse and rat. The N-terminal half of Pirin is significantly conserved between mammals, plants, fungi, and even prokaryotic organisms. Genomic Southern and Western blots demonstrate the presence of Pirin genes and their expression, respectively, in all mammalian cell lines tested. The expression pattern, the concentrated localization in subnuclear structures, and its interaction with NFI/CTF1 in the two-hybrid system classify Pirin as a putative NFI/CTF1 cofactor, which might help to gain new insights in NFI/CTF1 functions.

Amino Acid Sequence↗
PubMed1997

Effects of atrial natriuretic peptide on phagocytosis and respiratory burst in murine macrophages.

Atrial natriuretic peptide (ANP) is known to affect cardiovascular physiology displaying both hormone- and neurotransmitter characteristics. However, there is increasing evidence that ANP possesses additional biological activities referring to the immune system. To further strengthen this hypothesis the effect of ANP on two major functions of macrophages, i.e., phagocytosis and respiratory burst was tested. Both parameters were analyzed by flow cytometry employing bone marrow derived macrophages and the murine macrophage cell line J774. In both cell types preincubation with ANP dose dependently (10(-10)-10(-7) M) increases ingestion of opsonized fluorescent latex particles. The respiratory burst activity was monitored by oxidation of dihydrorhodamine-123 in cells stimulated either with phorbol-myristate (PMA, 10 ng/ml) or formyl-Met-Leu-Phe (fMLP, 1 microM). In both cases preexposure of cells to ANP (10(-8)-10(-6) M) for 2 h enhances reactive oxygen production. The data demonstrate an influence of ANP on important defense mechanisms of macrophages and thus extend the knowledge regarding the pharmacological profile of this natriuretic peptide.

Animals↗
PubMed1996

A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen.

We describe the phenotype of gene-targeted mice lacking the putative chemokine receptor BLR1. In normal mice, this receptor is expressed on mature B cells and a subpopulation of T helper cells. Blr1 mutant mice lack inguinal lymph nodes and possess no or only a few phenotypically abnormal Peyer's patches. The migration of lymphocytes into splenic follicles is severely impaired, resulting in morphologically altered primary lymphoid follicles. Furthermore, activated B cells fail to migrate from the T cell-rich zone into B cell follicles of the spleen, and despite high numbers of germinal center founder cells, no functional germinal centers develop in this organ. Our results identify the putative chemokine receptor BLR1 as the first G protein-coupled receptor involved in B cell migration and localization of these cells within specific anatomic compartments.

Animals↗
PubMed1996

A prospective risk analysis of contemporary thoracic surgery.

OBJECTIVE: The results of surgical therapy can only be accurately judged if the patients' characteristics and their impact on the outcome are known. The purpose of this study was to identify the risk factors of contemporary thoracic surgery, which could serve as a basis for a risk-matched comparison of different surgical techniques. METHODS: The data of 15 patients' undergoing thoracic surgery were prospectively documented. The outcome of the various operative procedures applied was statistically correlated with the access procedure, sex, age, body mass, dignity of underlying disease and six concomitant diseases. RESULTS: Four patients died within 30 days of surgery (mortality: 2.6%). Morbidity comprising all complications (class I) and morbidity comprising only complications of consequence for postoperative therapy (class II) rose with the number of concomitant diseases (50%/0% with no concomitant disease, 89%/33% with more than three concomitant diseases). Univariate testing identified malignant disease (P = 0.002), male sex (P = 0.003), body mass index of less than 20 and more than 27 kg/m of the expected level according to the Quetelet rule (P = 0.013) and a combination of concomitant respiratory and cardiocirculatory disease (P = 0.022) as being associated with class I morbidity. Male sex was significantly coincident with class II morbidity (P = 0.020). Logistic regression analysis demonstrated that these characteristics also had independent influence on class I morbidity (P = 0.022, P = 0.001, P = 0.023, P = 0.028). CONCLUSION: It is concluded that these characteristics are important predictors of morbidity of thoracic surgery. If a non-randomized comparison of the outcome of thoracic operations or different access strategies like thoracotomy or thoracoscopy is intended, at least these patient features should be documented and used as a basis for matching pairs.

Adolescent↗
PubMed1996

Laparoscopic and thoracoscopic surgery in infancy and childhood, the Münster/Gent experience.

Laparoscopic and thoracoscopic surgery have had a tremendous impact on adult surgery, but are still rarely used in children. In the past 3 years 168 children have been treated endoscopically in the three cooperating institutions. The course of all patients was documented prospectively in order to determine the value and prove the safety of endoscopic surgery in children. The operations performed endoscopically comprised appendectomy (n = 39), diagnostic procedures (24), adhesiolysis (n = 22), cholecystectomy (n = 13), bowel resection (n = 8), pyloromyotomy (n = 6), ovarial resection (n = 6), hiatus hernia repair (n = 22), splenectomy (n = 6), first stage of Fowler-Stephens operation for kryptorchidism (n = 3) and interruption of persistent botallic ducts (n = 6) in preterm infants. Apart from four wound infections (2.4%) following perforated appendicitis, one of which required laparotomy for perityphlitic abscess there were no serious complications. No patient died, and overall morbidity related to the procedure was 1.8% (i.e. incidence of uneventful minor intraoperative complications). Furthermore endoscopic surgery provides a better diagnostic survey of the abdomen or thorax so that missing of secondary pathology is unlikely. Pain and reflectory impairment of bowel-function or respiration were diminished, the aesthetic results were excellent and hospitalization could be reduced to a minimum. It is concluded that laparoscopic and thoracoscopic surgery are safe and reliable procedures for children and yield very encouraging results.

Adolescent↗
PubMed1995

A versatile flow cytometry-based assay for the determination of short- and long-term natural killer cell activity.

A flow cytometry based method has been developed to assess natural killer (NK) cell activity in both short-term (4 h) and long-term (18 h) NK assays. Target cells were either labeled with PKH-2, c'FDA or D275. Simultaneously, dead cells were identified by counter-staining with the nuclear dye propidium iodide. Using flow cytometry, only D275 in combination with propidium iodide permits the differentiation of four cell populations: live target cells, dead target cells, live effector cells, and dead effector cells. Even after the extended incubation periods (18 h) necessary for the determination of NK activity in some domestic animals these four populations remain clearly distinguishable. Comparison of results with cells of normal human individuals obtained using this D275/propidium iodide flow cytometry assay with data derived from fluorescence microscopy or an endogenous lactate dehydrogenase release assay shows a strong correlation. Since in long-term NK assays a high proportion of dead effector cells is constantly observed this cell population frequently limits the use of the lactate dehydrogenase release assay but does not interfere with the flow cytometry assay presented here. Using this novel assay, we have demonstrated the suppressive effects of defined glycosaminoglycans on long-term porcine NK activity.

Animals↗
PubMed1995

Organization of the alpha-globin promoter and possible role of nuclear factor I in an alpha-globin-inducible and a noninducible cell line.

Nuclear factor I (NFI) was suggested to be involved in the expression of the human alpha-globin gene. Two established cell lines, which express alpha-globin differentially, were therefore compared for differences in binding of NFI at the alpha-globin promoter in vivo. HeLa cells, in which alpha-globin is repressed, show a high density promoter occupation with several proteins associated with structurally distorted DNA. Cell line K562, which is inducible for alpha-globin, surprisingly was found to be heterogeneous consisting mainly of cells (approximately 95%) unable to express alpha-globin. However, the promoter of the nonexpressing K562 cells was clearly different from that of HeLa cells, being occupied only at basal transcriptional elements. Therefore, the alpha-globin gene in these K562 cells may not be truly repressed, but in an intermediate state between repression and active transcription. The NFI site of the alpha-globin promoter appeared occupied in HeLa but free of proteins in K562 cells. All cells of both cell lines produce NFI, but the composition and DNA binding affinity of NFI species differ significantly between the two cell lines. Therefore, distinct forms of NFI may repress alpha-globin transcription in HeLa cells. However, NFI is apparently not involved in establishing the latent transcriptional state of the majority of K562 cells.

Base Sequence↗