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R Kammerer

Publications and source records attributed to R Kammerer.

At least 19 recordsLinked to original sources
PubMed2001

Carcinoembryonic antigen-related cell adhesion molecule 1 on murine dendritic cells is a potent regulator of T cell stimulation.

Dendritic cells (DC) are important APCs that play a key role in the induction of an immune response. The signaling molecules that govern early events in DC activation are not well understood. We therefore investigated whether DC express carcinoembryonic Ag-related cell adhesion molecule 1 (CEACAM1, also known as BGP or CD66a), a well-characterized signal-regulating cell-cell adhesion molecule that is expressed on granulocytes, monocytes, and activated T cells and B cells. We found that murine DC express in vitro as well as in vivo both major isoforms of CEACAM1, CEACAM1-L (having a long cytoplasmic domain with immunoreceptor tyrosine-based inhibitory motifs) and CEACAM1-S (having a short cytoplasmic domain lacking phosphorylatable tyrosine residues). Ligation of surface-expressed CEACAM1 on DC with the specific mAb AgB10 triggered release of the chemokines macrophage inflammatory protein 1alpha, macrophage inflammatory protein 2, and monocyte chemoattractant protein 1 and induced migration of granulocytes, monocytes, T cells, and immature DC. Furthermore, the surface expression of the costimulatory molecules CD40, CD54, CD80, and CD86 was increased, indicating that CEACAM1-induced signaling regulates early maturation and activation of dendritic cells. In addition, signaling via CEACAM1 induced release of the cytokines IL-6, IL-12 p40, and IL-12 p70 and facilitated priming of naive MHC II-restricted CD4(+) T cells with a Th1-like effector phenotype. Hence, our results show that CEACAM1 is a signal-transducing receptor that can regulate early maturation and activation of DC, thereby facilitating priming and polarization of T cell responses.

Animals↗
PubMed2001

Approach to a multiparametric sensor-chip-based tumor chemosensitivity assay.

Although not widely practiced by oncologists, in vitro tumor chemosensitivity assays (TCA) have proved to increase the lifetime of tumor patients in prospective clinical trials. By individualizing cancer therapy, they can support the clinician's decision which is usually based on empirically retrieved data and thereby prevent inadequate chemotherapy. We present the first results of a new sensor-chip-based technology which might be useful for a multiparametric TCA. In particular, the aspect of dynamic on-line data generation on intact cellular specimens is a major difference to alternative assays. A series of experiments has been performed on cell lines and human tumor explants. Cell cultures and tumor tissue explants were placed on miniaturized silicon and glass sensor chips. The sensor data currently analyze metabolic profiles (rates of extracellular acidification and cellular oxygen consumption) and changes in cell morphology (monitoring of electric impedance). With the cell lines, drug-associated cellular signals have been detected with all three parameters, while primary explants so far caused metabolic responses only. In particular, cellular respiration or mitochondrial activity seems to be a most sensitive indicator of acute cytotoxic effects. The experimental results were achieved using different test versions. Besides giving a status report, the theoretical potential and current problems of sensor chip technology in TCA is discussed.

Acetaldehyde↗
PubMed1998

A distinct distribution of natural killer cell subgroups in human tissues and blood.

Natural killer (NK) cells have been subdivided according to their CD16/CD56 expression into at least 2 subgroups. We examined the distribution of these NK subgroups in humans. In the blood of normal individuals, CD16++/CD56+/CD3- NK cells predominate, constituting more than 90% of all NK cells. In contrast, decidua is infiltrated almost exclusively by CD16(+/-)/CD56+/CD3- NK cells (>90%), a fact so far seen in context with decidua being an immunoprivileged tissue. However, this NK subgroup can also be detected in the blood, where it comprises about 10% of NK cells. We have found that normal (colon) as well as neoplastic (ovarian and urothelial carcinoma) tissues are also predominantly infiltrated by this CD16+/- NK subgroup. Lymphatic fluid draining solid tissues contains CD16+/- NK cells exclusively, with absolute numbers of NK cells being very low. No predominating NK subgroup was seen in ascites. CD16+/- NK cells, when tested against the target cell lines K562 and JAR, revealed a cytotoxic spectrum different from CD16++ NK cells and from T cells. A change in the CD16/CD56/CD3 phenotype was not seen in either subgroup in long-term cultures containing IL-2 (1,000 U/ml). Our data indicate that the decidua is not the only solid tissue infiltrated by CD16+/- NK cells. Other normal and malignant tissues were also infiltrated predominantly by this NK cell subgroup. We suggest that CD16+/- NK cells represent a functionally distinct NK subgroup involved in the surveillance of solid tissues.

Body Fluids↗
PubMed1998

Biliary glycoprotein (CD66a), a cell adhesion molecule of the immunoglobulin superfamily, on human lymphocytes: structure, expression and involvement in T cell activation.

The biliary glycoproteins (BGP or CD66a), a group of different splice variants of a single gene, are members of the carcinoembryonic antigen family and the immunoglobulin superfamily. Recently, we detected CD66a on IL-2 activated lymphocytes. In this study we characterized the structure and the expression pattern of BGP on human lymphocytes and investigated its role in T cell activation. Lymphocytes express 2 of the 13 known splice variants, i.e. BGPa and BGPb, which are glycosylated in a lymphocyte-specific manner. Both BGPa and BGPb have the long cytoplasmic tail, which contains two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like motifs, but differ in their extracellular region containing 4 and 3 immunoglobulin-like domains, respectively. On PBL BGP is expressed in small amounts only on B cells and Th cells. Stimulation with IL-2 leads to a strong up-regulation of BGP by these cells, and induces de novo BGP expression on gammabeta T cells, CD8+ and CD56+ cells, but not on CD16+ lymphocytes. This up-regulation of BGP seems to be part of the physiological process of T cell activation, since stimulation with anti-CD3 mAb is sufficient to induce BGP up-regulation. Based on the presence of the two ITIM-like motifs, one may expect that BGP inhibits T cell activation, but surprisingly, engagement of BGP enhances the proliferation of anti-CD3-stimulated T cells.

Antigens, CD↗
PubMed1998

Isolated extracellular matrix-based three-dimensional in vitro models to study orthotopically cancer cell infiltration and invasion.

An initial event in colon cancer progression is the migration of epithelial cells through the basement membrane (BM) and the invasion of the colon submucosa, where tumour cells enter blood and lymph vessels to spread throughout the body. To interrupt this process would mean the prevention of metastasis. In order to investigate tumour cell invasion orthotopically in the human system, we established novel in vitro models which mimic normal human colon tissue (colon reproductions, CoRes) and primary colon carcinomas (artificial tumours, ArTs). These models are based on the isolated extracellular matrix (iECM) of the respective human tissues. Two isolation methods were established, the Digestion Method and the Lysis Method neither of which destroyed the characteristic architecture of the ECM found in the original tissues. BM components, i.e. laminin, fibronectin and collagen IV, were detectable in the iECM isolated with the Lysis Method but not those isolated with the Digestion Method. Scanning electron microscopic analysis of the normal colon iECM demonstrated that even if the BM was missing, the luminal surface consisted of densely packed ECM filaments which do not allow cell infiltration without degradation of the iECM. Furthermore, we demonstrated that iECM can be separately supplemented with different cell types, i.e. colorectal carcinoma cells, normal fibroblasts and immune cells at any desired concentration, combination and localisation. Therefore, these models could be used to determine the role of the BM and of the tumour cell/normal cell crosstalk in the infiltration process of human colorectal carcinoma cells.

Basement Membrane↗
PubMed1997

Modulations of the effector function and cytokine production of human lymphocytes by secreted factors derived from colorectal-carcinoma cells.

We investigated the in vitro effects of factors secreted by 3 freshly explanted human colorectal-carcinoma (CRC) cell lines on lymphocyte proliferation, IL-2-receptor expression, LAK-cell generation and cytokine secretion. We found that the supernatants of all 3 CRC cell lines inhibited T-cell proliferation in a dose-dependent manner, due to the secretion of immunosuppressive factors (ISFs). In addition, the supernatants of 2 cell lines were able to inhibit LAK-cell generation and to depress IL-2R, but not HLA-DR expression, on PHA-activated T cells. Furthermore, the secretion of cytokines, i.e., IFN-gamma, IL-1beta, IL-2 and TNF-alpha, by peripheral-blood mononuclear cells (PBMC) was differently modulated by the tumor-cell supernatants, e.g., the production of IFN-gamma was reduced in normal PBMC stimulated with PHA. However, the effects induced by the supernatants were not identical: for example, factors from one CRC cell line (w25) influenced early and late events of T-cell activation and division, while 2 others (w19 and te6) contributed only to the inhibition of early events. Some biochemical properties of the ISFs were characterized. Our results suggest that colon-tumor cells can secrete ISFs, which may lead to the in vivo immunosuppression often observed in patients with these tumors.

Colorectal Neoplasms↗
PubMed1996

The carcinoembryonic antigen (CEA) modulates effector-target cell interaction by binding to activated lymphocytes.

We and others have shown that the carcinoembryonic antigen (CEA) modulates the susceptibility of human colorectal carcinoma cells to cytotoxic lymphocytes. We now demonstrate that the density of the CEA molecules on the tumor cell surface has a determining influence on its protective function. In contrast, CEA released by tumor cells has no protective effect for CEA-negative cells. To elucidate the responsible mechanism, we analyzed the binding properties of CEA to lymphokine activated killer (LAK) cells. In agreement with our observation that only membrane-bound CEA provides protection, we found that intercellular contact between LAK cells and CEA-expressing tumor cells is required for binding of CEA to LAK cells. Using FACScan analysis, we demonstrate the presence of CEA on lymphocytes co-cultured with CEA-transfected cells but not after co-culture with their parental cells and after incubation with soluble CEA. Interestingly, following overnight co-culture the amount of bound CEA on LAK cells was identical regardless of adherence on tumor cells or loss of contact with tumor cells. This indicates that CEA is released from the tumor cells after binding to LAK cells. Our results suggest that tumor cells can modulate effector cell adhesion by regulating the turnover rate of CEA on the tumor cell membrane.

Carcinoembryonic Antigen↗
PubMed1996

Biliary glycoprotein (BGP) expression on T cells and on a natural-killer-cell sub-population.

Human T and natural-killer (NK) cells, that are thought to be the major cytotoxic effector-cell populations in the defence against neoplastic cells, were isolated from blood and decidua in order to analyze their expression of carcinoembronic-antigen-(CEA)-family-member proteins. Biliary glycoprotein (BGP,CD66a) was the only member of the carcinoembryonic antigen family detected. While freshly isolated T-cells expressed low amounts of BGP, freshly isolated NK cells were negative. After in vitro stimulation for 3 days, T cells up-regulated their BGP expression and a sub-group of NK cells (CD16- CD56+), known to predominate in decidua revealed de novo expression of BGP. In contrast, stimulated CD16+ CD56+ NK cells, which occur exclusively in the blood, remained negative. The expression of BGP could be shown on the protein level by using a panel of 12 well-defined MAbs and on the transcription level in rt-PCR and subsequent oligonucleotide hybridization. Interestingly, rIL-2-stimulated T cells expressed 3-fold higher levels of BGP compared with those seen after stimulation with phytohemagglutinin (PHA). PHA, on the other hand, induced a higher expression of HLA-DR, an activation marker of T cells. The differential regulation implies a distinct function of BGP and HLA-DR.

Antigens, CD↗
PubMed1995

The influence of the local environment on tissue architecture of colorectal carcinoma (CRC) cell aggregates and its consequence for tumour attack by lymphocytes in vitro and in vivo.

We analysed colorectal carcinoma (CRC) specimens, tumour cell spheroids and artificial tumours (ArTs) for tissue architecture, carcinoembryonic antigen (CEA) expression and lymphocyte infiltration. Two distinct organisation forms of well-differentiated CRC cells were found in vivo and in vitro. Tumour cells having contact with the tumour stroma in primary tumours, and tumour cells growing within a stroma-like structure in vitro (ArTs) were arranged as pseudoglands. In contrast, tumour cells grown as spheroids or tumour cells having lost contact with the tumour stroma in primary tumours, and most probably in the circulation, showed an inversion of the architecture of these pseudoglands, presenting their apical cell membrane to the environment. These different tumour cell formations affect lymphocytes attacking the tumour, which need contact with specific cellular membranes of polarised tumour cells, depending on the tumour architecture. Recently, we demonstrated that the CEA expression of CRC cells correlated with their resistance against LAK-cell lysis. Since CEA is mainly expressed on the apical membrane of the tumour cells, independent of the tissue architecture, the change from the pseudoglandular to the spheroid-like formation may represent an escape mechanism for malignant cells.

Carcinoembryonic Antigen↗
PubMed1995

Artificial tumor: a novel heterotypic, polymorphic, three-dimensional in vitro model of individual human solid tumors.

We established a new complex three-dimensional in vitro model called artificial tumor (ArT), which stimulates individual human solid tumors. In contrast to the generally used spheroid models consisting of tumor cells only, the model described in the present report is composed of both tumor cells and tumor stromal cells. We created ArTs as a replica of colon carcinomas, composed of colon carcinoma cells, colon fibroblasts, and as supportive skeleton fibrous tissue from human colon. All cellular components were established from the same surgically obtained colon carcinoma specimen. The ArTs studied came from 4 types of colon carcinomas; mucinous, well, moderately and undifferentiated colon carcinomas. Among all types of colon carcinomas ArTs could be established with a high rate of success, i.e. 81%. Cells growing for 5 days on the fibrous tissue under normal culture conditions formed tumors up to 2,000 microns in diameter. Morphological studies showed that tumor cells grown as ArTs maintained the individual characteristics of the original tumor; for example, a comparable heterogeneity in CEA expression and/or maintenance of the differentiation stage. Polarized tumor cells were linked with the tumor stroma-simulating structure by their basal cell membrane, and formed central lumina lined by the apical membranes of the tumor cells, a structure quite similar to the tissue architecture of colon carcinomas in vivo.

Cell Division↗
PubMed1994

CEA expression of colorectal adenocarcinomas is correlated with their resistance against LAK-cell lysis.

We have investigated the in vitro interaction of LAK cells with 20 different human tumor cell lines freshly isolated from colorectal carcinoma (CRC) specimens. Three steps of LAK cell/tumor cell interaction, namely adherence, infiltration and lysis, have been studied. All are important for the cytotoxic effect of LAK cells against solid tumors: LAK-cell adherence was studied on tumor-cell monolayer cultures, the infiltration capacity of LAK cells using tumor-cell spheroids and the resulting cytotoxic effects of LAK cells against CRC cells grown as spheroids or monolayers. Finally, we correlated the degree of lysis of the CRC cells with their carcinoembryonic antigen (CEA) production, the secretion of which varied in a broad range from not detectable to 2,800 ng/day in culture medium. Cytotoxicity experiments showed a good correlation between CEA expression of CRC cells and their resistance against allogeneic LAK cells. Spheroids of CEA-producing cells prevented LAK-cell infiltration resulting in high resistance against LAK-cell lysis. Adhesion of LAK cells on monolayers of CEA-expressing CRC cells was minimal. Our results indicate that CEA expression may be an escape mechanism protecting colon carcinoma cells from an attack by cytotoxic cells.

Carcinoembryonic Antigen↗
PubMed1990

[The results of radiotherapy of epicondylitis humeri using different dosages].

In a prospective analysis the effectiveness of roentgen irradiation with minimal doses (daily single doses .03 Gy up to a total dose of 1.5 Gy) was investigated in 207 patients with an epicondylitis humeri. Compared with a group of 92 patients, who were irradiated with higher doses being in general use (weekly 2x single doses 1.0 Gy to a total dose of 4.0 Gy), the therapeutic results show no significant differences. After termination of the first irradiation series an improvement of complaints was seen in half of the patients (48.8% or 50.0%). A further increase of the quota in success to 74.9% or 70.6% was found 6 weeks after termination of irradiation. By reason of radiotherapeutic results, mainly attained in chronic states of epicondylitis humeri after primary conservative therapy without success for months and partly surgical pretreatment, the radiotherapy should be used more frequently than till now, especially in consideration of its slight side-effects and injuries of patients.

Adult↗
PubMed1990

[Changes in the concentration of N-acetylneuraminic acid in the blood of patients with bladder cancer during radiotherapy].

The N-acetylneuraminic acid (N-ANA) concentration of serum in 24 patients with bladder carcinoma was measured with a modified Arzneibuch (D.L.) GDR-method before, during and after the postoperative radiotherapy. It was found that the N-ANA-concentrations in the patients operated resulted in a dependence from tumor staging already before the radiotherapy. The N-ANA concentration rose with increased staging. A temporary enhancement of the N-ANA-concentration with the maximum between 20. and 25 radiation fractions occurred in patients of staging T3 and relapses as well as with tumor cells being only little differentiated. The results are discussed in relation to the clinical importance.

Female↗
PubMed1989

Prevalence of antibodies to hepatitis C virus (HCV) in haemophiliacs.

The prevalence of 1) hepatitis C virus (HCV), an agent likely to be responsible for parenterally transmitted hepatitis non-A, non-B, 2) hepatitis B virus (HBV) and 3) human immunodeficiency virus (HIV) infection was studied in 211 patients with clotting disorders (78% of the patients had residual factor activities of less than or equal to 2%). Of these patients 71% were positive for HBV markers and 44% for HIV markers. Using a new ELISA technique, 80% were anti-HCV-positive. The prevalence of anti-HCV was greater in patients with more severe clotting disorders and was related to the total amount of replacement therapy received; the prevalence was less in older patients. Seroconversion after a single exposure to dry heat-treated factor concentrates was documented in 3 patients 3-4 months after exposure.

Factor VIII↗
PubMed1988

[Radiotherapy of induratio penis plastica].

From 1970 to 1986 forty-nine patients suffering from Induratio penis plastica (IPP) were treated by irradiation. It was used x-rays as soft-ray therapy and half-depth therapy, respectively, and fast electrons with an energy level ranged from 6 to 8 MeV. The follow-up observation time ranged from 8 months to 12 years. Very good to satisfactory results were obtained in 28 patients (57.1%). The treatment results were different clearly in dependence on the onset of symptoms and therapy, respectively. The possibilities of the irradiation therapy with lower side-effects and advantages as against other therapeutic approaches are described.

Electrons↗
PubMed1987

On-line analysis of rapid motion with a microcomputer.

A software package is described, which uses an Apple IIe computer with a digitizing board (Digisector 65) for analysing rapid motions of appendages of small insects from video images. Every 20 ms the program simultaneously analyses the position of two moving appendages after a background correction and the externally applied trigger stimulus. The data may be plotted in high-resolution plots with a matrix printer and evaluated with statistical methods.

Animals↗