PubMed Health⌕ Search

Biomedical subjects

R Förster

Publications and source records attributed to R Förster.

At least 19 recordsLinked to original sources
PubMed2005

[Resection of lung metastases--risk or chance?].

INTRODUCTION: The resection of pulmonary metastases can extend life of patients, even offering the possibility of cure. A risk analysis of the surgical procedure under the current practice of the thoracic surgery has been performed in this study. MATERIALS AND METHODS: Using a prolective method, data from 199 patients with 300 lung resections for pulmonary metastases done in our university department (1/1994-01/2003) were evaluated. Risk factors and therapy results were investigated in an uni- and multivariate analysis (Fishers Exact Test, Chi-Square and logistic regression). RESULTS: Overall lethality was 1 % and the total morbidity rate was 19 %. The 232 atypical resections were associated with 14 % morbidity rate, while the anatomical and combined ones were associated with 38 % (p = 0.0001). 19 patients revealed a FEV (1) < 1.6 l linked with a morbidity of 42 %. In patients without FEV (1) restriction morbidity was 18 % (p = 0.0172). Both, risk factors and the anatomical resection showed in the multivariate analysis a statistically significant increased morbidity. Additional risk factors (ASA > 2, age over 65, sex or cardial risk factors) did not influence postoperative morbidity. DISCUSSION: According to our data, no patient with good lung function should be withhold from atypical resection of pulmonary metastases offering the possibility of cure with low morbidity. However the indication should be critically evaluated if anatomical resection is required.

Aged↗
PubMed2002

[What is the cost of vascular operations? A prospective cost analysis of conventional and combined endovascular interventions].

Current and future legislation demand improved efficiency in the medical services. The aim of this study was to analyse the costs of vascular surgery in order to reveal potential ways of reducing expense. Taking into account the staff, equipment and operating theatre supplies, we analyzed 58 elective operations comprising 47 conventional and 11 combined endovascular procedures. The mean overall costs calculated for the different operations were: 5.269 DM for a transfemoral embolectomy (n = 3), 8.504 DM for a patchplasik of the profunda arteria (n = 8), 10.265 DM for a femoro-popliteal bypass with a prosthesis (n = 6)--13.180 DM with a vein (n = 2), 9.864 DM for conventional iliac artery reconstruction (n = 7)--iliac endovascular combined procedure (n = 4) 14.494 DM, 14.951 DM for a Y-prosthesis in case of stenosis (n = 3)--13.288 DM in case of infrarenal aortic aneurysm (IAA, n = 4), 11.954 DM for a tube prosthesis in case of IAA (n = 3), 23.571 DMY-stent prothesis for IAA (n = 5), 19.914 DM stent for a thoracic aneurysm (n = 2), 7.153 DM a carotid thrombendarterectomy (n = 6), 5.503 DM for varicosis surgery (n = 5). Because of the high cost of materials, the total outlay for combined endovascular procedures appeared to be high when compared to conventional vascular surgery. Substantial savings concerning the operation may only be achieved if facility structure and qualification of staff meets the particular requirements.

Adult↗
PubMed2001

CC chemokine receptor 7-dependent and -independent pathways for lymphocyte homing: modulation by FTY720.

Cognate interaction of chemokine receptor CCR7 on lymphocytes with its ligands CCL19 and CCL21 expressed on high endothelial venules (HEVs) is essential for effective migration of T and B cells across HEVs into secondary lymphoid organs. Plt mice, which lack expression of CCL19 and CCL21-ser, both ligands for CCR7 on HEVs, as well as CCR7-deficient mice, have a defective cell migration and reduced homing of lymphocytes. FTY720, a novel immunosuppressant, causes a reduction of lymphocytes in peripheral blood and tissues and their sequestration into lymphoid tissues. In this study we demonstrate that FTY720 rescues the homing defect in both CCR7(-/-) mice and plt mice. After FTY720 treatment, the number of CD4(+) and CD8(+) T cells as well as B cells in peripheral blood is reduced while pertussis toxin-sensitive homing into peripheral lymph nodes, mesenteric lymph node, and Peyer's patches is increased. Immunohistology demonstrates that FTY720 enables these cells to enter lymphoid tissue through HEVs. Thus, our data suggest an alternative G-alpha(i)-dependent, CCR7-CCL19/CCL21-independent mechanism for lymphocyte homing through HEVs which is strongly augmented in the presence of FTY720.

Animals↗
PubMed2001

Skewed maturation of memory HIV-specific CD8 T lymphocytes.

Understanding the lineage differentiation of memory T cells is a central question in immunology. We investigated this issue by analysing the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities and antiviral immune responses to HIV and cytomegalovirus. Ex vivo analysis of the expression of CD45RA and CCR7 antigens, together with in vitro analysis of the cell-division capacity of different memory CD8+ T-cell populations, identified four subsets of HIV- and CMV-specific CD8+ T lymphocytes, and indicated the following lineage differentiation pattern: CD45RA+ CCR7+ --> CD45RA- CCR7+ --> CD45RA- CCR7- --> CD45RA+ CCR7-. Here we demonstrate through analysis of cell division (predominantly restricted to the CCR7+ CD8+ T-cell subsets) that the differentiation of antigen-specific CD8+ T cells is a two-step process characterized initially by a phase of proliferation largely restricted to the CCR7+ CD8+ cell subsets, followed by a phase of functional maturation encompassing the CCR7- CD8+ cell subsets. The distribution of these populations in HIV- and CMV-specific CD8+ T cells showed that the HIV-specific cell pool was predominantly (70%) composed of pre-terminally differentiated CD45RA- CCR7- cells, whereas the CMV-specific cell pool consisted mainly (50%) of the terminally differentiated CD45RA+ CCR7- cells. These results demonstrate a skewed maturation of HIV-specific memory CD8+ T cells during HIV infection.

Adult↗
PubMed2001

Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype CD8+ T cells.

Inhibitory natural killer receptors (NKRs) such as killer cell immunoglobulin-like receptors (KIRs) in humans and Ly49 molecules in mice are expressed on NK cells and recognize multiple major histocompatibility (MHC) class I proteins. In humans and mice, a subset of CD8+ T cells also expresses NKRs and harbors a memory phenotype. Using mice that are transgenic for KIR2DL3 and its cognate HLA-Cw3 ligand, we show that engagement of inhibitory NKRs selectively drives the in vivo accumulation of a subset of memory-phenotype CD8+ T cells that express the beta chain of the interleukin 2 receptor. In vitro, recognition of MHC class I molecules by inhibitory NKRs on T cells down-regulated activation-induced cell death. These results unveil an MHC class I-dependent pathway that promotes the survival of a subset of memory-phenotype CD8+ T cells and also reveal an unexpected biological function for inhibitory NKRs on T cells.

Animals↗
PubMed2001

[Chances in surgical treatment of bronchial carcinoma under palliative conditions].

UNLABELLED: Palliative surgery aims at symptomatic relief in patients in whom curative therapy seems not feasible. When diagnostic imaging techniques describe advanced stage IIIa, IIIb or IV malignancy, despite of palliative intention curative resection may still be possible. Objective of the present study was to investigate lung cancer patients undergoing surgery with palliative intent and to compare their prognosis with patients whose tumor resection had been complete (R0) or incomplete (R1/R2). PATIENTS AND METHOD: Patients were assigned to one of the three groups on the basis of the following criteria: palliative intention with subsequent complete resection (group I, n = 11); curative intention with subsequent incomplete resection (group II, n = 38), palliative intention with incomplete resection (group III, n = 23). Additionally 3 patients were operated on by explorative thoracotomy. A total number of 75 patients was therefore investigated. Median follow-up period was 34.5 months. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The following procedures involving resection of pulmonary tissue were performed: pneumonectomy (n = 10), extended pneumonectomy (n = 32), lobectomy (n = 5), extended lobectomy (n = 11), sleeve lobectomy (n = 7), bilobectomy (n = 3), extended bilobectomy (n = 4). The 30 days hospital mortality rate was 13%. Median survival times were 25.5 months in group I, 12.8 months in group II and 7.7 months in group III (statistical significance: group I vs. group II/III, p < 0.05). CONCLUSIONS: Results of the present study show that patients with bronchial carcinoma in advanced tumor stages III and IV may still benefit from pulmonary resection, particularly when reduction of their somatic complaints is considered. In 11 patients, R0 resection was feasible leading to a statistically significant prolongation of their survival rates.

Adenocarcinoma↗
PubMed2000

Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production.

Chemokines and their receptors have been identified as major regulators controlling the functional organization of secondary lymphoid organs. Here we show that expression of CXC chemokine receptor 5 (CXCR5), a chemokine receptor required for B cell homing to B cell follicles, defines a novel subpopulation of B helper T cells localizing to follicles. In peripheral blood these cells coexpress CD45RO and the T cell homing CC chemokine receptor 7 (CCR7). In secondary lymphoid organs, CD4(+)CXCR5(+) cells lose expression of CCR7, which allows them to localize to B cell follicles and germinal centers where they express high levels of CD40 ligand (CD40L), a costimulatory molecule required for B cell activation and inducible costimulator (ICOS), a recently identified costimulatory molecule of the CD28 family. Thus, when compared with CD4(+)CD45RO(+)CXCR5(-) cells, CD4(+)CD45RO(+)CXCR5(+) tonsillar T cells efficiently support the production of immunoglobulin (Ig)A and IgG. In contrast, analysis of the memory response revealed that long-lasting memory cells are found within the CD4(+)CD45RO(+)CXCR5(-) population, suggesting that CXCR5(+)CD4 cells represent recently activated effector cells. Based on the characteristic localization within secondary lymphoid organs, we suggest to term these cells "follicular B helper T cells" (T(FH)).

Antibody Formation↗
PubMed2000

A chemokine-driven positive feedback loop organizes lymphoid follicles.

Lymphoid follicles are B-cell-rich compartments of lymphoid organs that function as sites of B-cell antigen encounter and differentiation. CXC chemokine receptor-5 (CXCR5) is required for B-cell migration to splenic follicles, but the requirements for homing to B-cell areas in lymph nodes remain to be defined. Here we show that lymph nodes contain two types of B-cell-rich compartment: follicles containing follicular dendritic cells, and areas lacking such cells. Using gene-targeted mice, we establish that B-lymphocyte chemoattractant (BLC/BCA1) and its receptor, CXCR5, are needed for B-cell homing to follicles in lymph nodes as well as in spleen. We also find that BLC is required for the development of most lymph nodes and Peyer's patches. In addition to mediating chemoattraction, BLC induces B cells to up-regulate membrane lymphotoxin alpha1beta2, a cytokine that promotes follicular dendritic cell development and BLC expression, establishing a positive feedback loop that is likely to be important in follicle development and homeostasis. In germinal centres the feedback loop is overridden, with B-cell lymphotoxin alpha1beta2 expression being induced by a mechanism independent of BLC.

Animals↗
PubMed2000

NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue.

Targeted disruption of the transcription factor NKX2.3 gene in mice results in anatomical defects of intestine and secondary lymphoid organs. Here, we report that spleen and Peyer's patches of NKX2. 3-deficient mice are considerably reduced in size and lack the ordered tissue architecture. T and B cells are misplaced within the spleen and mesenteric lymph nodes and fail to segregate into the appropriate T and B cell areas. Furthermore, splenic marginal zones, characterized by specific B cells and various types of macrophage-derived cells around the marginal sinus, are absent in mutants. Homozygous NKX2.3 mutants lack the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that is normally expressed in mucosa-associated lymphoid tissue (MALT) and spleen. We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly, suggesting that MAdCAM-1 is at least partly responsible for the migration and homing defects of lymphocytes and macrophages in mutants. Therefore, expression of MAdCAM-1 seems to be required for building functional structures in spleen and MALT, a prerequisite for unimpaired migration and segregation of B and T cells to and within these organs.

Animals↗
PubMed2000

CXCR5-deficient mice develop functional germinal centers in the splenic T cell zone.

The chemokine receptor CXCR5 is thought to be essential for the migration of B cells into the network of follicular dendritic cells in the spleen. However, as shown here, B cells and follicular dendritic cells do co-localize, albeit aberrantly, even in the absence of CXCR5. In mice lacking CXCR5 both cell types are found in a broad ring around the sinuses of the marginal zones. Upon immunization with the T cell-dependent antigen 2-phenyl-oxazolone, ectopic germinal centers develop in the periarteriolar lymphocyte sheath. A network of follicular dendritic cells forms in the vicinity of the central arteriole within which the antigen-activated B cells proliferate. The analysis of the expressed V gene repertoire revealed that during B cell proliferation, hypermutation is activated and V region genes accumulate somatic mutations. The pattern of somatic mutations suggests that affinity selection may occur. This analysis confirms that in CXCR5-deficient mice, the organization of splenic primary follicles is severely impaired. However, within the T cell zone a micro-environment is built up, which provides all requirements needed for the affinity maturation to take place.

Animals↗
PubMed1999

Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers.

Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte-associated molecule 4-immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.

Abatacept↗
PubMed1999

Two subsets of memory T lymphocytes with distinct homing potentials and effector functions.

Naive T lymphocytes travel to T-cell areas of secondary lymphoid organs in search of antigen presented by dendritic cells. Once activated, they proliferate vigorously, generating effector cells that can migrate to B-cell areas or to inflamed tissues. A fraction of primed T lymphocytes persists as circulating memory cells that can confer protection and give, upon secondary challenge, a qualitatively different and quantitatively enhanced response. The nature of the cells that mediate the different facets of immunological memory remains unresolved. Here we show that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets. CCR7- memory cells express receptors for migration to inflamed tissues and display immediate effector function. In contrast, CCR7+ memory cells express lymph-node homing receptors and lack immediate effector function, but efficiently stimulate dendritic cells and differentiate into CCR7- effector cells upon secondary stimulation. The CCR7+ and CCR7- T cells, which we have named central memory (TCM) and effector memory (TEM), differentiate in a step-wise fashion from naive T cells, persist for years after immunization and allow a division of labour in the memory response.

Cells, Cultured↗
PubMed1999

CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.

The proper function of immune surveillance requires well-coordinated mechanisms in order to guide the patrolling immune cells through peripheral tissues and into secondary lymphoid organs. Analyzing gene-targeted mice, we identified the chemokine receptor CCR7 as an important organizer of the primary immune response. CCR7-deficient mice show severely delayed kinetics regarding the antibody response and lack contact sensitivity and delayed type hypersensitivity reactions. Due to the impaired migration of lymphocytes, these animals reveal profound morphological alterations in all secondary lymphoid organs. Upon activation, mature skin dendritic cells fail to migrate into the draining lymph nodes. Thus, in order to bring together lymphocytes and dendritic cells to form the characteristic microarchitecture of secondary lymphoid organs, CCR7 is required to rapidly initiate an adoptive immune response.

Animals↗
PubMed1999

Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells.

When naive T lymphocytes are activated and differentiate into memory/effector cells, they down-regulate receptors for constitutive chemokines such as CXCR4 and CCR7 and acquire receptors for inflammatory chemokines such as CCR3, CCR5 and CXCR3, depending on the Th1/Th2 polarization. This switch in chemokine receptor usage leads to the acquisition of the capacity to migrate into inflamed tissues. Using RNase protection assays, staining with specific antibodies, and response to recombinant chemokines, we now show that following TCR stimulation, memory/effector T cells undergo a further and transient switch in receptor expression. CCR1, CCR2, CCR3, CCR5, CCR6 and CXCR3 are down-regulated within 6 h, while CCR7, CCR4, CCR8 and CXCR5 are up-regulated for 2 to 3 days. Up-regulation of CCR7 following TCR stimulation was observed also among resting peripheral blood T cells and required neither co-stimulation nor exogenous IL-2. On the other hand IL-2 down-regulated CXCR5, up-regulated CCR8 and facilitated the recovery of CCR3 and CCR5. Upon TCR stimulation, Th1 and Th2 cells produced comparable sets of chemokines, including RANTES, macrophage inflammatory protein-1beta, I-309, IL-8 and macrophage-derived chemokine, which may modulate surface chemokine receptors and contribute to cell recruitment at sites of antigenic recognition. Altogether these results show that following TCR stimulation effector/memory T cells transiently acquire responsiveness to constitutive chemokines. As a result, T cells that are activated in tissues may either recirculate to draining lymph nodes or migrate to nearby sites of organized ectopic lymphoid tissues.

Base Sequence↗