Biomedical subjects

H Tesch

Publications and source records attributed to H Tesch.

153 records · Page 9Linked to original sources

PubMedDate not supplied

IL6 and IL6 receptor expression in Burkitt's lymphoma and lymphoblastoid cell lines: promotion of IL6 receptor expression by EBV.

We have analysed a panel of different Burkitt's lymphoma (BL) and lymphoblastoid cell lines (LCLs) for the expression of IL6 and IL6 receptor (IL6R). Epstein-Barr-Virus (EBV) positive or negative BL cell lines and the corresponding lymphoblastoid cell lines (LCL), derived from EBV immortalized mononuclear cells of the BL patients, were tested for the expression of IL6 mRNA and protein by Northern blot experiments and ELISA, and for the expression of the IL6R mRNA and protein by Northern blot Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and flow cytometry. Our results demonstrate that six out of 19 Burkitt's lymphoma cell lines produced IL6 constitutively. All three cell lines infected with the EBV substrain B95-8 (B95-8 convertants) produced IL6, in contrast to the original EBV negative lines and to the cell lines infected with the EBV substrain P3HR1 (P3HR1 convertants). The produced IL6 was biologically active as shown by proliferation of the IL6 dependent cell line TEPC 1033 C2. The two BL cell lines with the highest level of IL6 production (190 pg/ml and 550 pg/ml) expressed in addition IL6R molecules on the cell surface. Monoclonal antibodies directed against IL6 did not inhibit the growth of these two BL cell lines, thus excluding autocrine stimulation in these lines. IL6R expression could be further demonstrated in all LCLs analysed, in five out of seven EBV positive BLs and two out of three B95-8 convertants, but only in one out of the six EBV negative BL cell lines. Our results suggest that EBV in immortalized B cells and in Burkitt's lymphoma cells can promote IL6 receptor expression.

Base Sequence↗

PubMedDate not supplied

CD3 x CD19 bispecific antibodies and CD28 costimulation for locoregional treatment of low-malignancy non-Hodgkin's lymphoma.

In advance of using bispecific antibodies for the treatment of B cell lymphoma in humans, we analysed CD3 x CD19 bispecific antibodies for their capacity to induce T cell activation in cell suspensions from follicular lymphoma lymph nodes. Here, we demonstrate that the lack of costimulatory molecules, such as members of the B7 family, on the tumour cells resulted in insufficient activation of autologous T lymphocytes. However, stimulation and proliferation of T cells could be induced by addition of monospecific CD28 antibodies. Moreover, we show that bispecific CD3 x CD19 antibodies can protect severe combined immunodeficiency (SCID) mice from human Epstein-Barr-virus (EBV)-induced B cell lymphoma growth. In these in vivo studies, CD28 costimulation did not show a significant benefit, possibly because of the high-level expression of CD80 and CD86 on the surface of the lymphoma cells. Furthermore, the treatment of SCID mice with bispecific antibodies, with or without CD28 antibodies, induced tumour-protective effects, as determined by a rechallenging experiment in long-term-surviving animals with the autologous EBV-transformed tumour B cell line. Treatment of a follicular lymphoma patient by intratumoural injection of both antibodies resulted in immunological responses with increases in the T/B ratio of peripheral blood as well as enhanced NK cell activity without toxic systemic side-effects.

Animals↗

PubMedDate not supplied

Abdominal lymphoma staging: is MR imaging with T2-weighted turbo-spin-echo sequence a diagnostic alternative to contrast-enhanced spiral CT?

PURPOSE: To evaluate the diagnostic value of MR imaging in abdominal lymphoma staging, in comparison with that of the established spiral CT, within the context of a prospective study. METHODS: 50 patients with non-Hodgkin (n = 27) and Hodgkin lymphoma (n = 23) were examined with a plain T2-weighted TSE sequence (parameters: TE 90 ms, TR >2.500 ms, slice thickness 8 mm, slice interval 0.8 mm, ETL 20, NEX 4), and with spiral CT following oral and intravenous administration of contrast agent. RESULTS: Both CT and MR imaging agreed in showing abdominal lymphomas in 34/50 cases. The size of the detected lymphomas was between 1.5-9 cm (mean: 4.3 +/-2.2 cm). In the analysis of the individual lymph node sites, CT showed involvement of the paraaortic lymph nodes in 29/50 patients, compared with 28/50 in MRI, and involvement of the portal lymph nodes in 15/50, compared with 12/50. Both techniques showed the iliac lymph nodes in 21/50 patients, the inguinal lymph nodes in 10/50, and the mesenteric lymph nodes in 11/50. Both techniques also showed focal organ lesions in 12/50 cases. CONCLUSIONS: In the staging of abdominal lymphomas, MR imaging with a T2-weighted TSE sequence can be regarded as equal to spiral CT in the detection of lymph adenopathy and the demonstration of focal organ lesions. In addition to the absence of ionizing radiation, the advantage of MR imaging is that there is no necessity for oral or intravenous administration of contrast agent.

Abdominal Neoplasms↗

PubMedDate not supplied

Semiautomated and simultaneous analysis of the interleukin-10 gene microsatellites IL-10G and IL-10R by fluorescence-based polymerase chain reaction reveals significant differences in allele distributions between Caucasians (Germany) and Africans (Gabon).

Interleukin-10 (IL-10) is an important immunoregulatory cytokine influencing many aspects of the adaptive and inflammatory immune response. Two dinucleotide repeats have been identified in the 5'-UTR of IL-10 and shown to be useful genetic markers in several diseases. A simple, two-colour fluorescence assay was developed for determination of microsatellite fragment length by an automatic sequencer. Using this method polymorphisms at the IL-10G and IL-10R loci of the 5' flanking region of the IL-10 gene can be identified simultaneously. A unified standard nomenclature was applied to the known IL-10G and IL-10R microsatellites. The multiplex PCR approach was used to compare the allele frequencies in two independent donor groups from Germany (Caucasian), comprising 112 and 106 cases, respectively, and one group from Gabon (African) including 91 donors. Significant differences in the allele distribution were found. Both Caucasian populations tested showed no significant differences in their allele and genotype distribution. Whereas in Africans, allele IL-10G25 is rare at 3% compared to 21% in Caucasian, alleles IL-10G22 and G23 are more prevalent in Africans than in Caucasians (22% versus 10% and 26% versus 7%, respectively). Within the IL-10R locus, the allele R13 was observed at 88% in the African group compared to 69% in Caucasians. These data may help immunogenetic studies in diseases, where IL-10 is thought to be deregulated.

Alleles↗

PubMedDate not supplied

Rearrangements of immunoglobulin- and BCR-genes in chronic myeloid leukemia.

Clonal rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes have been demonstrated in malignant lymphoid tumors of B and T cell origin. In Philadelphia chromosome (Ph1) positive chronic myeloid leukemia (CML) the bcr and c-abl genes are reorganized and a new transcript, composed of both genes is expressed. Immunoglobulin gene rearrangements were also detected in lymphoid blast crisis but not in myeloid blast crisis of CML. We analyzed in Southern blot experiments whether Ig and TCR rearrangements could also occur in the chronic or accelerated phase of the disease. Our results indicate that immunoglobulin but not TCR delta or TCR gamma gene rearrangements also occurred in some patients with CML in chronic and accelerated phase but not in myeloid blast crisis, together with rearrangements of the bcr gene.

Adult↗

PubMedDate not supplied

Persistent active herpes virus infection associated with atypical polyclonal lymphoproliferation (APL) and malignant lymphoma.

This study focuses on lymphoproliferative diseases associated with persistent infection by Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6). A suggestive premalignant lymphoproliferative state is distinguished from malignant lymphoma and identified as "atypical polyclonal lymphoproliferation" (APL). Sixteen cases of herpes virus (HHV)-associated APL are compared with 21 cases of HHV-associated malignant lymphomas (ML), with 108 cases of EBV or HHV-6 related acute infections mononucleosis, with 14 cases of seronegative non-specific lymphoid hyperplasia and with 304 cases of HHV-unrelated ML. Six cases of APL and two ML occurred in AIDS patients, two cases in Sjogren's syndrome, one in a kidney allograft recipient, and the remaining cases had no identified underlying disease. APL was histologically reminiscient of excessive infectious mononucleosis, while other cases of Castleman's disease or even of malignant lymphoma. Seropositive APL and ML contained significantly more virus genome than is found in latent background infection. There was no histologic difference between HHV-6 or EBV-positive APL or ML, although both viruses infect different lymphocyte populations. From histology alone, seropositive ML cases were not distinguished from seronegative ones, yet persistent active EBV and HHV-6 appear to predominate in follicular center cell- and immunoblastic lymphoma and in HOdgkin's disease. Although no a direct oncogenic activity of these viruses could be observed in our cases, they may contribute to lymphomagenesis by inducing progressive lymphoproliferation.

Adolescent↗

PubMedDate not supplied

Monoclonal B cell proliferation in lymphoproliferative disease associated with herpes virus type 6 infection.

Clonal gene rearrangements and aneuploidy are commonly recognized as characteristics of malignancy. We challenge this by an observation of a 3 1/2 year old boy with chronic benign lymphadenopathy, connatal splenomegaly and peripheral lymphocytosis. His brother and mother suffered from similar disease without progression. Cervical lymph node biopsy from our patient revealed a benign histology corresponding to the clinical course; however, clonal rearrangements of the JH and TCR gamma gene were demonstrated in lymph node cells and DNA aneuploidy in 11% of bone marrow cells. Immunohistology showed an inverse T-helper/T-suppressor cell ratio with polyclonal B cell increase and extensive lymphocyte activation. In situ hybridization demonstrated foci of lymphoid cells in the paracortical zone with expression of herpes virus type 6 genome. In addition, the patient, his brother and his mother showed serological evidence of active infection with the human herpes virus-6 (HHV-6). The association of HHV-6 infection, monoclonality and benign lymphoproliferation is discussed.

Antibody Formation↗

PubMedDate not supplied

Human herpesvirus-6 (HHV-6) in Hodgkin's disease: cellular expression of viral antigens as compared to oncogenes met and fes, tumor suppressor gene product p53, and interleukins 2 and 6.

Patients with Hodgkin's disease (HD) frequently show elevated serum titers against human herpersvirus-6 (HHV-6) and their tissues contain significantly increased numbers of cells with HHV-6 DNA. This may coincide with similar data of Epstein-Barr virus (EBV) infections. According to in vitro studies, Hodgkin- and Reed-Sternberg (RS) cells can be infected by HHV-6 and may be coinfected by HHV-6 and EBV. Both viruses are potentially oncogenic and also may interfere with the production of various cytokines. We now demonstrate by using immunohistological methods that HHV-6 antigens are present in 77.3% of the HD lymphomas, 37% of which contain the replication-associated p41 "early-late" antigen and 63% the late membrane antigen complex gp116/64/54. Monocytic cell populations including HD and RS cells are most frequently antigen-positive, while lymphoid cells are less frequently. These cells also express IL-6 and IL-6 receptors as well as the IL-2 receptor a chain (CD25), while only occasionally the IL-2 receptor beta chain (p70). IL-6 receptors are significantly more frequently expressed than IL-6 itself. HD and RS cells constitute a significant pool of proliferating cells as reflected by their 95% positivity for PCNA, yet tumor suppressor genes are found in only 21% and the proto-oncogenes fes and met are expressed in various types of cells. The data may indicate that both viruses possibly contribute to the course of the disease through polyclonal stimulations of cell proliferation and coincident dysregulation of the cytokine network control of cell function and proliferation. A direct oncogenic effect of EBV and HHV-6 in HD appears less probable.

Adolescent↗

PubMedDate not supplied

Semi-quantitative in situ hybridization and immunohistology for antigen expression of human herpesvirus-6 in various lymphoproliferative diseases.

Fifty patients with various hyperplastic and malignant lymphoproliferative diseases were investigated for evidence of human herpesvirus-6 infection. Virus DNA and antigen expression was investigated in lymph node biopsies by in situ hybridization and immunohistology and was correlated with data of immunophenotyping. Supplemental immunoglobulin- and T cell receptor gene rearrangement studies were used to support the classification of the proliferative lymphoid lesion. Elevated numbers of cells carrying HHV-6 DNA and/or antigens were found in cases of Hodgkin's lymphoma and follicular center cell non-Hodgkin's lymphoma as well as atypical polyclonal lymphoproliferation (APL), yet not in reactive lymphoid hyperplasia and in most other lymphomas. Immunophenotyping showed that virus -infected cells were primarily lympho-histiocytic elements, less frequently Hodgkin's- and Reed-Sternberg cells, and not malignant B lymphocytes as in follicular center cell lymphomas. This suggests that the virus is rather not the causative oncogen in these cases, yet does not exclude a cocarcinogenic effect of it during the development and ths course of uncontrolled lymphoproliferation.

Antigens, Viral↗