Biomedical subjects

B F Odermatt

Publications and source records attributed to B F Odermatt.

At least 37 records · Page 2Linked to original sources

PubMed1993

Molecular analysis of the LMP (latent membrane protein) oncogene in Hodgkin's disease.

Molecular analysis of the LMP (latent membrane protein) oncogene was performed in 21 Epstein-Barr virus (EBV) positive cases of Hodgkin's disease (HD) with proven LMP gene expression. In each case, viral DNA of the LMP gene was assessed for polymorphism (deletions, insertions, mutations) by polymerase chain reaction (PCR) amplification with selected primers. Specificity of the amplified targets was proven by internal oligonucleotide hybridisation and nested primer PCR. Homogeneity of the 5' LMP gene region coding for the amino terminal, transmembrane, and short extracytoplasmic domains of the protein was identified in all cases. However, deletions or insertions of small DNA sequences within the coding region for the intracytoplasmic LMP domain were observed in about 20% of cases. In one of them, a 30-base-pair deletion was precisely localized by DNA sequencing. A particularly high frequency of DNA polymorphism (30% of cases) was found in the 3' untranslated LMP region. However, when analysing the LMP gene in seven benign conditions, no DNA polymorphism was found. These data suggest conservation of oncogenic LMP regions coding for the protein domains known to be associated with transforming capacities and immunogenic functions. They also show a considerable genomic heterogeneity of the coding region for the intracytoplasmic domain and the 3' untranslated mRNA region. This LMP DNA polymorphism identified within a localized (Swiss) population suffering from HD is unexpected. Its eventual clinical significance remains to be determined.

Antigens, Viral↗

PubMed1992

Expression of human recombination activating genes (RAG-1 and RAG-2) in Hodgkin's disease.

The differentiation status of Sternberg-Reed (SR) cells is still not well defined, primarily because of their scarcity in tumor biopsies of Hodgkin's disease (HD). In this study we have determined the genomic differentiation status of SR cells by quantitation of recombinase activating gene (RAG) expression. RAG genes are selectively transcribed in immature lymphoid cells. In B cells they are silent after genomic rearrangement has occurred, whereas in T cells they are downregulated during positive selection of double-positive thymocytes into single-positive cells. RNA from tumor biopsies either with numerous (11 cases) or a with few SR cells (16 cases) was assessed by a sensitive reverse transcriptase polymerase chain reaction (RT-PCR) and the results compared with established positive and negative controls. In all except two cases levels of RAG expression were within the range of those determined in negative controls. In both positive cases and in the positive control RAG mRNA was further quantitated by competitive PCR. In cases with abundant SR cells RAG expression was still below that observed in 10(-2) dilutions of positive controls. These results suggest that SR cells are derived from lymphoid cells, more differentiated than the pre-B or common thymocyte stage, which have already undergone genomic rearrangement. They show the value of assessing RAG expression by RT-PCR in the characterization of lymphoid malignancies.

Animals↗

PubMed1992

Significance of the detection of Epstein-Barr virus DNA in lymph nodes in patients with Hodgkin's disease.

Epstein-Barr virus (EBV) DNA is frequently identified in benign and malignant lymphoproliferative conditions. As shown by in situ hybridization studies viral DNA is localized within malignant cells as well as benign lymphocytes. Clonal and nonclonal EBV genomes are present in Hodgkin's disease (HD), lymphomas of the immunocompromised host and reactive lymph node hyperplasia. Lytic infection with formation of linear genomes is observed in the same conditions but appears to be infrequent in HD as shown by quantitation of mRNA coding for viral capsid antigen. Expression of the oncogene LMP (latent membrane protein) is seen in Sternberg-Reed (SR) cells and immunoblasts of AIDS-related lymphoma and infectious mononucleosis (IM). In HD, the region of the BNLF1 oncogene coding for the amino terminal and transmembrane domains (associated with oncogenic function) of LMP appears to be homogeneous whereas the region coding for the intracytoplasmic (carboxy terminal) domain of LMP is heterogeneous. Cytological similarities between SR cells and immunoblasts of IM and AIDS-related lymphomas are consistent with the hypothesis that the BNLF1 oncogene is one possible inducer of morphological features of SR cells. Whether chromosomal integration of EBV DNA is an important factor in activation of such a transforming activity remains to be elucidated. EBV DNA positive and negative HD cases with numerous SR cells lack significant mRNA expression of the two recombinase activating genes (RAG-1 and RAG-2). Therefore the SR cells appear to be derived from lymphocytes beyond the pre-B-cell or common thymocyte stage which may or may not subsequently become infected by EBV.

Antigens, Viral↗

PubMed1992

[T-cell rich B-cell lymphoma associated with hemophagocytic syndrome].

Report of a T-cell rich B-cell lymphoma (TCRBCL) in a 43 years old man with an associated haemophagocytic syndrome (HS). At presentation the haemophagocytic cells involved the same organs as the lymphoma, i.e. spleen, liver, abdominal lymph nodes and bone marrow. As supportive measure to alleviate chemotherapy-induced granulocytopenia the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was given. After an initial improvement of the blood granulocyte count pancytopenia developed again, resulting in fatal sepsis. Autopsy demonstrated massive proliferation of macrophages in the bone marrow with haemophagocytosis as morphological correlation to the pancytopenia. The observation that exogenous GM-CSF enhanced the preexistent HS primarily reactive to the TCRBCL raises the question if endogenous GM-CSF may play a role in triggering a HS. The observed association of TCRBCL and HS has not been reported so far.

Adult↗

PubMed1992

[Demonstration of Epstein-Barr virus DNA and determination of immunoglobulin and T-cell receptor gene rearrangerments in diagnostic lymph node biopsies from patients with Hodgkin's disease].

Lymph node biopsies of 52 patients with Hodgkin's disease were analyzed by Southern blot hybridization for the presence of monoclonal rearrangements of immunoglobulin and T cell receptor genes. The same tissues were tested for Epstein-Barr virus DNA by the polymerase chain reaction using four different sets of primers. Monoclonal rearrangements were identified in only four tumors, whereas Epstein-Barr virus was present in 79% of biopsies. A correlation between the degree of infiltration by Reed-Sterberg cells, clonality and the presence of Epstein-Barr virus could not be found. These results are in agreement with similar studies reported in the literature. The nature of the malignant cell in Hodgkin's disease and the role of Epstein-Barr virus in the etiology of this tumor remains to be established.

Base Sequence↗

PubMed1991

Frequent detection of Epstein-Barr virus DNA by the polymerase chain reaction in lymph node biopsies from patients with Hodgkin's disease without genomic evidence of B- or T-cell clonality.

This study of 52 Swiss patients with Hodgkin's disease (HD), including 17 cases with a high content of Sternberg-Reed (SR) and Hodgkin (H) cells, was performed to determine the percentage of cases harboring Epstein-Barr virus (EBV) DNA and/or clonal rearrangements of Ig and T-cell antigen receptor (TcR) genes in diagnostic lymph node biopsies. Special attention was drawn to the heavily infiltrated cases to detect a possible relationship between clonality and EBV DNA identification. EBV DNA was detected by the polymerase chain reaction (PCR) using three different sets of specific primers. The viral origin of the amplification products was confirmed by hybridization with a radiolabeled internal probe or demonstration of a specific Sma I restriction site. Genomic rearrangement of Ig and TcR genes was studied by Southern blot analysis. EBV DNA was identified by PCR in 38 of 48 cases (79%). Clonal rearrangements were identified in only 4 of 52 cases (Ig genes) and were independent of the degree of infiltration by SR cells and the presence of EBV DNA. The absence of EBV DNA in three cases with numerous SR cells (only one of them showed clonal rearrangement) and the presence of only a few viral copies in four further cases with numerous SR cells (semiquantitative analysis of viral DNA by PCR was performed in 26 EBV-positive cases) suggests that this virus is modulating rather than an etiologic agent in a considerable proportion of HD cases.

B-Lymphocytes↗

PubMed1991

Tenascin Mr 220,000 isoform expression correlates with corneal cell migration.

The three isoforms of chicken tenascin, an extracellular matrix glycoprotein, are generated by alternatively spliced fibronectin type III domains. The resulting proteins migrate as bands of Mr 220,000 (ten220), Mr 200,000 (ten200) and Mr 190,000 (ten190) on SDS-PAGE. We describe here two monoclonal antibodies, one specific for ten220 (mAb T17) and another that recognizes all isoforms (mAb T16). These were used to examine the differential expression of isoforms during development. Most impressive is the close correlation between ten220 expression and cell migration in the embryonic cornea. Initially (stage 18), ten190/200 can be detected within the corneal epithelium and along the basement membranes of the lens and sclera. Ten220 appears within the primary stroma immediately prior to the invasion by neural-crest-derived cells. This expression is maintained during the subsequent migration of fibroblasts from the conjunctiva into the primary stroma. With the completion of migration and the marked increase in matrix synthesis by corneal fibroblasts, ten220 disappears. Ten190/200 remains in the region adjoining the endothelium, the Bowman's membrane and the adjacent stroma. The cell-migration-associated isoform is isolated from extracts of embryonic tissues as a homohexamer. Low molecular weight forms appeared absent but a new tenascin band of Mr 210,000 could be detected in brain extracts which may be a new isoform. We conclude that the synthesis of tenascin isoforms is under tight developmental control and speculate that a function of the additional domains is to facilitate cell migration.

Animals↗

PubMed1991

[Virus induced acquired immunodeficiency: correlation with T cell mediated destruction of spleen and lymph node architecture].

Mice infected with the non-cytopathic lymphocytic choriomeningitis virus (LCMV) develop a severe acquired immune suppression. This is caused by the elimination of virus infected antigen presenting cells by cytotoxic T cells leading to a severe destruction of the follicular organization of lymphoid organs. The impairment of immune functions may allow the virus to establish persistent infections in initially immunocompetent hosts.

Animals↗

PubMed1991

Phlebosclerosis: disorder or disease?

Morphological examinations were performed in a total of 318 subjects (168 men and 150 women). Electron microscopic and immunohistological examinations were added in selected cases. Phlebosclerosis is a fibrotic degeneration of the venous wall that is regularly found in non-varicose veins of aged persons. Although its incidence is age-related, no correlation exists between degree and age. Marked degrees may occasionally occur already below the age of twenty. Both sexes and all the superficial leg veins (various levels of the long saphenous vein and minor venous branches) are likewise affected. The intima of the superficial leg veins is predominately involved, but media and adventitia may also be affected. Although the morphological appearance is similar to that of arteriosclerosis, localization, progression and clinical consequences are different. Phlebosclerosis of superficial leg veins is a disorder of little direct clinical consequence, but may have an indirect influence on the wall contractility. In the deep leg veins, however, a distinct phlebosclerosis of the intimal layer may be responsible for the development of thrombosis. As a secondary alteration, phlebosclerosis may complicate varicose veins (fibrous degeneration of wall areas with tortuosity, ectasia and smooth muscle atrophy). These lesions may further impair the already deficient reflux function. However, phlebosclerosis is no prerequisite but a late sequel of varicosis.

Adult↗

PubMed1990

Detection of Epstein-Barr virus DNA by polymerase chain reaction in lymph node biopsies from patients with angioimmunoblastic lymphadenopathy.

Epstein-Barr virus DNA was detected by the polymerase chain reaction (PCR) in five lymph node biopsies from eight patients with diagnosis of angioimmunoblastic lymphadenopathy (AILD). Three pairs of specific primers detected EBV DNA sequences near the 5' end (Bam W region), the middle (BMRF 1 region) and the 3' end (Eco RI D region) of the viral genome with equal accuracy when 1 microgram of DNA and 30 amplification cycles were used. When only 100 ng of DNA were screened with the BMRF 1 set of primers, a specific amplification product was still identifiable. The 593 base pair amplification product obtained using the Eco RI D set of primers was shown to contain an expected Sma I site at position 215, confirming the viral origin of the amplified sequence [corrected]. Our findings indicate that lymph nodes of AILD patients frequently harbour the entire EBV genome at a high percentage of at least 1 viral copy per 15,000 human cells.

Base Sequence↗

PubMed1990

[Phenotypic and genotypic characterization of splenic infiltrates in hairy cell leukemia].

Cells of splenic infiltrates of five patients with hairy cell leukemia have been analyzed for the expression of immunoglobulin by immunohistochemistry and for rearrangement of T cell receptor and immunoglobulin genes by the Southern blot technique. In each case surface immunoglobulins were found with monoclonal expression of light chains. Concomitantly, heavy and light chain gene rearrangements were present. These results confirm the B cell nature of hairy cells.

Blotting, Southern↗

PubMed1990

[Pattern of intermediate filaments in thymomas].

The cytokeratin pattern of medullary, mixed and cortical thymomas and thymic carcinomas were analyzed by two-dimensional equilibrium electrophoresis. Extracts from a medullary thymoma and normal, total thymi showed a similar pattern. On the other hand in cortical thymomas and very similar in thymic carcinomas there were marked changes in the cytokeratin pattern. These findings support the classification of thymomas as described by MULLER-HERMELINK.

Electrophoresis, Gel, Two-Dimensional↗

PubMed1989

[Hairy cell leukemia: study of genomic rearrangements in splenic infiltration].

Genomic DNA extracted from heavily infiltrated spleens of 5 patients with hairy cell leukaemia was hybridized with genomic probes for immunoglobulin genes. The rearrangement pattern, correlating well with the immunohistochemical findings, was that of a clonal B-cell proliferation in all cases. Analysis of the lambda light chain genome with two different probes enabled more accurate localization of the clonal rearrangements within this genome. A small additional T-cell population identified in 3 cases was immunogenotypic of polyclonal (reactive) nature.

DNA Probes↗

PubMed1989

Polyclonal rearrangements of the T-cell receptor beta-chain in fatal angioimmunoblastic lymphadenopathy.

Genomic rearrangement of germline T-cell antigen receptor (TcR) and immunoglobulin (Ig) genes was studied by Southern blot analysis in seven patients with angioimmunoblastic lymphadenopathy (AILD). In three cases clinically suspected of transformation into malignant lymphoma, hybridization with the TcR beta probe showed markedly dimished intensity in the 11.5 kb germline band after Eco RI digestion and normal germline configuration after Hind III and Bam HI digestion, indicating polyclonal T cell rearrangements. A clonal rearrangement of the TcR beta gene was detected in only one case at initial biopsy. No monoclonal rearrangement of Ig genes was observed. These data show that in some cases of AILD disease progression is indicated by polyclonal TcR rearrangements and not by outgrowth of a malignant clone, supporting the concept of AILD as an immunoregulatory disorder.

Blotting, Southern↗

PubMed1988

Immunohistological evaluation of endothelial markers and basement membrane components in port-wine stains.

As shown by an immunohistological study, the endothelial cells in the lesions of port-wine stains (PWSs), investigated for factor VIII-related antigen and Ulex europaeus agglutinin I lectin, were found to be swollen or flattened corresponding to mild or pronounced dilatation of vessels, respectively. Furthermore, dilated vessels in the lesional skin exhibited a broader staining for type IV collagen, laminin and fibronectin, which, however, was not considered to be of primary pathogenetic importance for vessel dilatation in PWSs. As concluded from the number of vessels, no vascular proliferation occurred, which indicates that PWS is not a true hemangioma but a special clinical type of telangiectasia.

Adolescent↗

PubMed1987

[Provisional treatment results of intensive combination chemotherapy (m-BACOD) in non-Hodgkin lymphoma of intermediate and high malignancy].

10 patients with diffuse large cell lymphoma were treated with 10 cycles of m-BACOD. 7 patients presented with a pathological stage IV, 2 with a clinical stage III and one with a clinical stage II disease. 8 patients have been in complete remission for 3-21 months (mean 9 months) after completion of therapy. One patient with T-immunoblastic lymphoma and bulky mass died of progressive disease after 6 cycles of m-BACOD. A second patient with T-immunoblastic lymphoma relapsed 24 months after completion of therapy. Treatment-related major complications, especially MTX-related ulcerative stomatitis, did not occur.

Adult↗

PubMed1987

Diagnostic and prognostic value of monoclonal antibodies in immunophenotyping of angioimmunoblastic lymphadenopathy/lymphogranulomatosis X.

Immunophenotyping of frozen lymph node sections from seven patients with morphologically defined angioimmunoblastic lymphadenopathy (AILD) was performed with a panel of 20 monoclonal antibodies (MoAb). MoAb for identification of dendritic reticulum cells showed remnants of follicular structures in all cases. In four cases these 'burnt out' follicular structures were associated with clusters of polyclonal B-cells. Vascular proliferation and small amounts of intercellular collagenous fibrils were reliably revealed by MoAb CIV22 against basement membrane collagen. Cellular infiltrates of T4+ cells prevailed in four cases, of T8+ cells in one case. In one case conventionally identified blasts were of T- and B-cell origin. Expression of cell proliferation associated nuclear antigen identified by MoAb Ki-67 was present in more than 25% of lymph node cells in three patients with fatal outcome, but in less than 10% of cells in two patients with a better clinical course. Therefore MoAb Ki-67 may represent a valuable prognostic marker in AILD.

Adolescent↗

PubMed1987

Diagnostic and prognostic value of monoclonal antibodies in immunophenotyping of T cell lymphomas.

6 cases of post-thymic T cell lymphoma (PTCL) and 4 cases of T lymphoblastic lymphoma were investigated with a panel of 21 monoclonal antibodies (MoAb). The PTCL group was composed of 2 by 2 cases of lymphoepithelioid cell lymphoma, T zone lymphoma and T immunoblastic lymphoma. In lymphoepithelioid cell lymphoma, the cell proliferating activity was low, and a malignant clone was not identifiable by the methods used. In the cases of T zone lymphoma and T immunoblastic lymphoma, malignant populations were detectable on the grounds of immunologic marker profile combined with cytologic particularities. The 4 cases of T lymphoblastic lymphoma were of a common cortical thymic phenotype (T4+, T8+, T6+) and presented with a mediastinal mass. In 3 of them, cell proliferation marker (Ki-67) was expressed by most tumor cells. Cell proliferating activity, however, did not inversely correlate with survival.

Adolescent↗