Biomedical subjects

J Langner

Publications and source records attributed to J Langner.

At least 55 records · Page 3Linked to original sources

PubMed1997

Constitutive expression of HLA class II mRNA in synovial fibroblast-like cells from patients with rheumatoid arthritis .

We describe the quantification of the absolute amounts of HLA class II mRNA and class II transactivator (CIITA) mRNA by competitive reverse transcription polymerase chain reaction in cultured synovial fibroblast-like cells (SFC) of patients with rheumatoid arthritis. High basal levels of transcription of class II mRNA (10(7)-10(9) molecules/microgram total RNA) and CIITA mRNA were detected in cultured SFC, with DPB < DRB = DQB, although SFC only express small amounts of MHC class II proteins. In contrast to SFC, we did not detect class II mRNA nor CIITA mRNA in skin fibroblasts. After treatment with IFN-gamma, we observed a 3- to 28-fold increase in class II mRNA in SFC and an increase of DRB and DPB in skin fibroblasts from undetectable levels to 10(8)-10(9) molecules/microgram total RNA.

Arthritis, Rheumatoid↗

PubMed1997

Cyclotetrapeptides and cyclopentapeptides: occurrence and synthesis.

The structures reported for the three cancerostatic all-L-cyclotetrapeptides cyclo(Pro-Leu)2, cyclo(Pro-Val)2 and cyclo(Pro-Phe)2 isolated from a tunicate seem questionable. The synthetic compounds claimed to be identical to the naturally occurring cyclotetrapeptides are in fact not cyclotetrapeptides but rather cyclooctapeptides. We have not been able to prepare the tyrosinase inhibitor cyclo(Pro-Val-Pro-Tyr). Ring closure of H-Pro-Val-Pro-Tyr-OC6F5 gave rise to 31% of cyclo(Pro-Val-Pro-D-Tyr). The same product was obtained in 53% yield from H-Pro-Val-Pro-D-Tyr-OC6F5. For the ring closure to the all-L-cyclopentapeptide cyclo(Pro-Ala-Ala-Phe-Leu), all ring closure positions have been investigated. The reaction at the nitrogen atom of leucine leads to 21% of the all-L-cyclopentapeptide. Dimers or mixtures of monomers and dimers result from reaction at all other positions.

Amides↗

PubMed1997

Phenotypic analysis of T lymphocytes isolated from non-small-cell lung cancer.

BACKGROUND: The study of the nature of tumor-infiltrating lymphocytes (TIL) may provide insight into the complex issue of tumor-host interactions. METHODS: Cytofluorometric analysis was performed to characterize the phenotypic profiles of TIL from non-small-cell lung cancers (NSCLC) and pulmonal metastases of different primary locations. An extensive panel of antibodies was used specific to different activation-associated molecules on T cells. In 10 patients, findings on the T cell phenotype of TIL were compared with the findings in peripheral blood lymphocytes (PBL) from the same patients. Furthermore, we investigated whether the measurement of the TIL phenotype might serve as a prognostic parameter correlating with survival of patients with NSCLC. RESULTS: In contrast to PBL, T cells infiltrating lung tumors expressed significantly higher amounts of various activation antigens. However, the immunophenotype of TIL hardly differed among different histological subtypes and pulmonal metastases. Addressing the prognostic value of the lymphocytic composition of TIL, we found no significant difference in the survival of NSCLC with high or low percentages of T and natural killer cells, whereas high percentages of B cells were associated with increased survival (p = 0.05). Patients with high percentages of CD13+ tumor-infiltrating T cells had significantly poorer prognosis according to Cox's multivariate analysis. CONCLUSION: Our results indicate that different tumor histologies within the lung are characterized by a 'similar' T cell phenotype, at least with respect to the surface molecules studied by us. The measurement of the expression of activation-associated markers on T cells may have prognostic value in the pathological evaluation of NSCLC.

Adult↗

PubMed1996

Treatment of fibroblast-like synoviocytes with IFN-gamma results in the down-regulation of autotaxin mRNA.

In an effort to isolate genes that change expression at the mRNA level during treatment of fibroblast-like synoviocytes (SFC) with IFN-gama, we performed a differential display analysis. Here, we report the isolation of a cDNA clone corresponding to a 3.1 kb mRNA species that is reduced in synoviocytes after culture with IFN-gama. Sequence analysis revealed the 211 bp length cDNA clone to be identical to the motility-stimulating 125 kDa protein autotaxin (ATX). The down-regulation of ATX mRNA was confirmed by Northern blot analysis as well as competitive RT-PCR. SFC express 1 ng ATX mRNA/microgram total RNA. IFN-gama down-regulated ATX mRNA up to 50% as compared to control. Our results add a new finding to the manifold functions described for IFN-gama in rheumatoid arthritis.

Base Sequence↗

PubMed1996

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia.

The major histocompatibility complex is one of the interactive factors in the multifactorial model of carcinogenesis. Its main influence in experimental models is on the age at onset of malignancies. We have previously shown a similar effect of homozygosity for HLA-DR53 in CML. In the present study, we investigated 79 patients with CLL and 329 local controls from Germany. In addition to full serotyping, all patients and 116 of controls were also typed by HLA-DRB PCR analysis. The homozygosity rates for DR53 in patients under and over the median age (60 years) were 18.6% and 2.9%, respectively (p = 0.03). Eight of the 9 homozygous patients were under the median age. The sex ratio in the DR53 homozygous group was reversed in favour of females. The homozygosity rates for DR53 were different in the overall groups of patients and controls, yielding a relative risk (RR) of 2.4 (p = 0.03). This association was stronger in the early-onset group compared to age-matched controls (RR = 4.4; p = 0.008) and for females with an early onset compared to age- and sex-matched controls (RR = 17.9; p = 0.0008). The simultaneous occurrence of the alleles of the haplotype A2B62DR4 showed a strong association with CLL (RR = 4.1; p = 0.002). This was probably the reason behind the association with HLA-DRB1*0401 (RR = 2.4; p = 0.009). Compared to the accelerating effect of HLA-DR53, HLA-DR52 showed a significant delaying effect on the onset of CLL. These findings confirmed the influence of the HLA complex on the development of another leukaemia.

Adult↗

PubMed1996

Prognostic value of the immunomonitoring of patients with renal cell carcinoma under therapy with IL-2/IFN-alpha-2 in combination with 5-FU.

After tumor nephrectomy, patients suffering from metastatic renal cell carcinoma (RCC) received interleukin-2 (IL-2), interferon (IFN)-alpha-2b and 5-fluorouracil (5-FU) in one to three treatment cycles over 8 weeks. Using flow cytometry, we investigated the immunophenotype of peripheral blood lymphocytes from 22 patients during therapy. In all patients, we found an increase in the absolute number of T lymphocytes, especially of the CD4 type, and in the number of HLA-DR+, CD25+ T cells and natural killer (NK) cells. The mean number of B cells did not increase during therapy. The numbers of CD4+, CD8+ and CD25+ T cells correlated significantly with the clinical response. In addition, we found that the pretherapeutic number of T lymphocytes and B cells but not of NK cells was significantly higher in patients with a therapy-induced clinical response. In conclusion, we describe the predictive value of the number of lymphocytes from peripheral blood for the efficiency of IL-2/IFN-alpha-2b therapy in combination with 5-FU in patients with metastatic renal cell carcinoma.

Adult↗

PubMed1995

Stimulation of the expression and the enzyme activity of aminopeptidase N/CD13 and dipeptidylpeptidase IV/CD26 on human renal cell carcinoma cells and renal tubular epithelial cells by T cell-derived cytokines, such as IL-4 and IL-13.

Aminopeptidase N (APN) and dipeptidylpeptidase IV (DPIV) are transmembrane type II molecules widely distributed in mammalian tissues. In recent years, the interest in cell surface peptidases has increased considerably because, among other things, several reports indicate roles of ectopeptidases in tumour cell metastasis. Investigations into the regulation of APN and DPIV on tumour cells are rare. We report, for the first time, that IL-4 and IL-13 can up-regulate protein expression as well as enzymatic activity of both the peptidases on renal carcinoma cells and renal tubular epithelial cells in culture. The analysis of mRNA by competitive polymerase chain reaction (PCR) confirmed our results with respect to the APN increase at the level of gene expression. IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) augmented the IL-4-induced effect with respect to APN but not to DPIV. A 5-day incubation with interferon-gamma (IFN-gamma) increased protein expression, especially of APN and, to a lesser extent, also of DPIV, whereas no significant increase in enzymatic activity could be observed. Small concentrations of transforming growth factor-beta 1 (TGF-beta 1) inhibit the expression and enzyme activity of DPIV. IL-6, IL-7, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been found to be without any effect on APN and DPIV. For a prospective therapeutic regimen with T cell-derived cytokines it has to be considered that--besides their effect on tumour cell growth--cytokines might affect surface ectopeptidases involved in tumour cell adhesion processes. The inhibition of APN and DPIV could be a new approach to suppression of cancer spread.

Base Sequence↗

PubMed1994

Expression of aminopeptidase N/CD13 in tumour-infiltrating lymphocytes from human renal cell carcinoma.

We have previously demonstrated the expression of aminopeptidase N (APN, CD13) on synovial T cells from patients with different forms of arthritis. T cells of peripheral blood and serous body fluids are CD13-negative but can be stimulated to express CD13 after activation, e.g., with Con A. In the present report, double-labelling and flow cytometry analyses were performed to characterize the phenotype of tumour-infiltrating lymphocytes (TIL). A large panel of antibodies specific for different activation-associated molecules on T cells was used. In contrast to TIL of lung cancer, TIL of renal cell carcinoma (RCC) consisted of significantly higher percentages of T cells expressing CD13, dipeptidylpeptidase N (DPIV, CD26) and HLA-DR, whereas T cells of lung cancer expressed more CD25, CD69 and CD54/ICAM1. No differences could be found in the expression of CD45RO, CD49a/VLA-1 and CD62L/L-selectin. Our results demonstrate that T cells in RCC and lung cancer differ in their phenotype, especially with respect to surface aminopeptidases. Investigations into the function of APN on T cells could be of help in gaining deeper insight into tumour defence as well as into general mechanisms of T cell functions.

Adenocarcinoma↗

PubMed1994

Characterization of the immunophenotype and functional properties of fibroblast-like synoviocytes in comparison to skin fibroblasts and umbilical vein endothelial cells.

We characterized the immunophenotype as well as functional properties--phagocytosis, the uptake of acetylated LDL, and the expression of HLA class II antigens, adhesion molecules, and cytokine mRNA--of fibroblast-like synoviocytes from rheumatoid arthritis synovium. Skin fibroblasts (FB) and umbilical vein endothelial cells (HUVEC) were studied in parallel. Cytofluorometric immunophenotyping by use of 84 mAb and 2 lectins and immunofluorescence microscopy indicated a high degree of homology between the three cell types. Only staining with mAb to von Willebrand factor (vWF) and CD31 and the lectin UEA-I appeared specific to HUVEC, whereas the mAb 5B5 to prolyl 4-hydroxylase that has been reported to be specific to FB stained HUVEC as well as synoviocytes and FB. All of the cells phagocytosed fluorescent latex beads of 1.7 and 2.6 microns in size. The uptake of acetylated LDL could be shown by HUVEC and, surprisingly, by synoviocytes, but not by FB. The induction of HLA-DR, -DP, and -DQ by IFN-gamma on the three cell types showed a similar dose-dependence. The upregulation of ICAM-1 by IL-1 alpha, TNF-alpha, and IFN-gamma appeared similar, whereas the induction of VCAM-1 by IL-1 alpha, IL-4, TNF-alpha, and IFN-gamma showed differences between the three cell types. ELAM-1 was expressed only on HUVEC after treatment with IL-1 alpha and TNF-alpha. The capacity of the cells to produce cytokines was studied at the level of mRNA by reverse transcription and PCR. All three cell types expressed the mRNA of IL-1 alpha, IL-6, IL-8, GM-CSF, and TGF-beta 1 spontaneously or after LPS stimulation, but never TNF-alpha mRNA. Our results indicate a high degree of relationship between the three cell types. In contrast to HUVEC, none of the markers and functional properties investigated appear specific to FB. Therefore, the issue of the origin of fibroblast-like synoviocytes and the role of vascular endothelial cells in the inflamed synovium is discussed.

Antibodies, Monoclonal↗

PubMed1994

Immunophenotype of lymphocytes in pericardial fluid from patients with different forms of heart disease.

Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the pericardial fluid (PF) from 127 patients undergoing open cardiac operation (heart valve disease, congenital heart defects, chronic ischemic heart disease). Macrophages and T cells represented the dominant cell types. Similar to T cells of body fluids other than peripheral blood, a high percentage of PF T cells expressed CD45RO and activation-associated molecules such as HLA-DR, CD69, CD54 and CD26. Surprisingly, we could demonstrate a very high proportion of CD11b+ T cells in PF. Furthermore, a significant proportion of PFT cells expressed aminopeptidase N/CD13. PF was further analyzed for the presence of IL-6, TGF-beta as well as TNF-alpha. IL-6 levels were low (undetectable to 4,500 U/ml), TGF-beta levels ranged from < 3 ng/ml up to 80 ng/ml, and TNF-alpha levels from < 3 pg/ml to 233 pg/ml. These findings show evidence of the presence of activated lymphocytes with a special immunophenotype as well as multiple cytokines in PF of patients with different forms of heart disease.

Adolescent↗

PubMed1994

[HLA and selective IgA deficiency].

A selective deficiency of IgA is developed significantly (p < 0.05) more frequently by HLA-A2-negative than by HLA-A2-positive healthy persons. The frequent combination of A1/A3 is absent. The incidence of HLA-B8-positive persons is increased (p < 0.01). A selective disadvantage is discussed.

Gene Frequency↗

PubMed1993

Demonstration of CD13/aminopeptidase N on synovial fluid T cells from patients with different forms of joint effusions.

Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the synovial fluid (SF) and the peripheral blood (PB) from patients suffering from juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA). The most obvious difference could be found in expression of the surface protease aminopeptidase N (AP N/CD13). Whereas monoclonal antibodies specific to CD13 failed to reveal surface expression on lymphocytes of the PB; 63 +/- 15% of SF T cells gave positive staining for CD13 using Leu-M7. No correlation between CD13 expression and joint disease could be found in patients who had different types of inflammatory joint effusions. CD13 expression of T cells was also found in synovial tissue and inflammatory serous cavity effusions. Fixation of T cells revealed the presence of intracellular CD13 antigen already located in the PB T cells of healthy individuals. Induction of CD13 expression on PB T cells could be demonstrated after incubation with Con A/IL-2 or SF from patients with RA. Our findings suggest a role for AP N as a new activation-associated molecule of T lymphocytes.

Aminopeptidases↗

PubMed1991