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G Ott

Publications and source records attributed to G Ott.

At least 73 records · Page 4Linked to original sources
PubMed1999

Exclusive detection of the t(11;18)(q21;q21) in extranodal marginal zone B cell lymphomas (MZBL) of MALT type in contrast to other MZBL and extranodal large B cell lymphomas.

Extranodal mucosa-associated lymphoid tissue (MALT)-type lymphomas and nodal and splenic marginal zone B cell lymphomas (MZBL) share morphological and immunophenotypic features with marginal zone B cells of reactive lymphoid tissues. Although displaying a similar immunophenotype, recent investigations suggest fundamental genetic differences among these subgroups. To determine the prevalence of the t(11;18) in a larger series of MALT-type lymphomas and to investigate a possible occurrence in other lymphomas, we screened 106 non-Hodgkin's lymphomas (NHL) by interphase cytogenetics using yeast artificial chromosome (YAC) probes flanking the breakpoint at 11q21. A signal constellation indicating a disruption in 11q21 and thus pointing to the presence of the t(11;18) was observed in 9 of 33 (27%) low-grade lymphomas of MALT type. The complete absence of t(11;18)-positive cells in 32 primary and secondary extranodal high-grade lymphomas suggests that low-grade lymphomas of MALT type characterized by the t(11;18) are unlikely to transform into high-grade tumors. The absence of tumor cells carrying the t(11;18) in nodal MZBL challenges the assumption that most, if not all, of these tumors represent the nodal manifestation of a so far undetected low-grade lymphoma of MALT type. The t(11;18) was not detected in a single case of 29 splenic MZBL investigated. This observation strengthens the view that splenic MZBL are biologically different from extranodal MZBL of MALT type.

Chromosome Banding↗
PubMed1999

Expression of costimulatory molecules in low-grade mucosa-associated lymphoid tissue-type lymphomas in vivo.

B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type develop against a background of chronic inflammation and have functional autoantigen receptors. Because they respond to environmental factors in vivo, the expression of costimulatory molecules, which play a key role in the differentiation of normal B-lymphocytes and in T-/B-cell interaction, may be critical in early MALT-type lymphoma pathogenesis until further chromosomal aberration leads to progression. We found a high number of tumor-infiltrating T-lymphocytes (TITLs) in all low-grade MALT-type lymphomas. The TITLs in low-grade lymphomas were activated and expressed a memory and immunocompetent phenotype. Reverse transcriptase-polymerase chain reaction analyses and immunohistochemistry confirmed the presence of CD40-ligand and Fas-ligand in 80% of low-grade lymphomas. In contrast to the TITLs, the tumor B cells did not express CD40-ligand or Fas-ligand in vivo or in vitro. Moreover, the cytokine profile in vivo suggested a Th2/Th3-weighted profile (interleukin-10, interleukin-13, transforming growth factor beta(1)) rather than Th1-weighted (interferon-gamma, interleukin-2). By interphase fluorescence in situ hybridization analysis the translocation t(11;18)(q21;q21) was found in four of nine (44%) cases studied. Interestingly, there was a four times higher proliferation and survival rate of purified t(11;18)-positive tumor B cells in vitro, although there were no significant profile differences from the TITLs in vivo. The finding of essential costimulating molecules in low-grade MALT-type lymphomas in vivo indicates a locally directed cognate T-/B-cell interaction. Consequently, a potentially equipped inflammatory background may not only determine the fate of autoreactive B-cells, but is also crucial to lymphoma maintenance and progression.

B-Lymphocyte Subsets↗
PubMed1999

Intranasal immunization of mice with influenza vaccine in combination with the adjuvant LT-R72 induces potent mucosal and serum immunity which is stronger than that with traditional intramuscular immunization.

Immunization of mice by the intranasal route with influenza virus hemagglutinin in combination with the mutant Escherichia coli heat-labile enterotoxin R72 (LT-R72) induced significantly enhanced serum and mucosal antibodies, surpassing, in most cases, responses achieved by traditional intramuscular immunization using inactivated split influenza vaccine. Furthermore, intranasal immunization with LT-R72 induced a potent serum immunoglobulin G2a response, indicating that this adjuvant has Th1 character.

Administration, Intranasal↗
PubMed1999

[MALT-type non-Hodgkin's lymphoma: advances in biopsy diagnosis and pathogenesis].

Malignant Non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue display unique morphological and biological features. Unlike the situation in nodal lymphomas, they almost invariably arise from defined and recognisable precursor lesions, such as chronic infections or autoimmune diseases. From the diagnostic point of view, efforts have been undertaken to define (1) the minimal requirements for the unequivocal diagnosis of MALT-type lymphoma, (2) the regression stages after Helicobacter pylori eradication, and (3) to establish a grading system for the respective lesions. Of importance, it must be emphasized that in most cases the biopsy received in first-line is not enough in establishing a correct diagnosis with regard to biological and therapeutic implications. In particular, the accurate estimation of the biological aggressiveness of the tumour will in most cases require extensive rebiopsies. As in nodal tumours, the genetic constitution of low grade MALT-type lymphomas is more and more revealed. While data on the importance of numerical aberrations are conflicting, certain structural aberrations, such as the t(1;14) and the t(11;18), have been unequivocally linked to MALT-type lymphomas. Preliminary data suggest that these aberrations may target the apoptotic pathway. Their recognition may herald the evolution of new tumour features, such as independence from outer regulatory influences, obviously in early stages determined by the microenvironment and might be closely related to the site of tumour development and hence be a feature of the primary inflammatory disorder.

Biopsy↗
PubMed1998

Dendritic cells internalize vaccine adjuvant after intramuscular injection.

Vaccine adjuvants help antigens elicit rapid, potent, and long-lasting immune responses. The lack of understanding of the immunological mechanism of action of adjuvants has limited the rational development of vaccines for human use. In particular, little is known about how the immune system processes adjuvants. The goal of the present study was to determine the fate of the vaccine adjuvant MF59, labeled with the fluorescent dye Dil, after injection with fluorescein-labeled gD2 antigen from type 2 herpes simplex virus. At 3 h after intramuscular injection into BALB/c mice, most of the MF59 was still in the form of extracellular droplets in the muscle, but a detectable fraction of the MF59 was in cells in the subcapsular sinus of draining inguinal lymph nodes. At 48 h, most of the MF59 at the site of injection was inside cells that were immunoreactive for the dendritic cell markers DEC-205 and MHC class II molecules, reflecting the interaction of MF59 with antigen presenting cells. At this time, intracellular MF59 was also abundant in the paracortical (T cell) region of lymph nodes. The gD2 antigen was also intracellular in muscle and colocalized MF59 at 48 h, and the presence of MF59 increased the amount of intracellular antigen. Similarly, serological antibody titers to gD2 were 207-fold higher after two injections when MF59 was administered with the antigen. These findings suggest that MF59 interacts with antigen presenting cells at the site of injection and then moves to the draining lymph nodes, where it increases the efficiency of antigen presentation to T cells.

Adjuvants, Immunologic↗
PubMed1998

Differentiation of low-grade non-Hodgkin's lymphomas using paraffin sections by image processing.

In a previous study, we were able to demonstrate that the differentiation of low-grade non-Hodgkin's lymphomas (NHLs) using digital image analysis of touch imprints obtained from native tumor tissue is feasible. The availability of touch imprints in routine diagnostics, however, is restricted. Therefore, we extended our studies toward paraffin sections being used as routine material for histological diagnoses. To identify five types of NHL classified according to the Revised European American Lymphoma classification, paraffin sections (n=53) of NHL and 9 reactive lymphoid tissues (RLTs) were scanned with a color-video-based microscope system and analyzed by digital image processing. A reliable division between benign and neoplastic lymphoproliferations was achieved. We were able to identify 78% of RLTs as benign and 94% of NHLs as neoplastic. The average probability of correct identification into the six subgroups was 66%. In detail, 78% of RLTs, 50% of chronic lymphocytic lymphomas and MALT-type lymphomas, 72% of mantle cell lymphomas, and 67% of follicle center cell lymphoma were classified correctly. Although the method of subclassifying or identifying NHLs on the basis of a computer-mediated assay is still not usable in daily practice, we show that a reliable differentiation between reactive and neoplastic lymphoproliferative lesions can be achieved by analysis of paraffin sections with high-resolution image analysis and that it is possible to define nuclear structures by identifying subtypes of NHL.

Diagnosis, Differential↗
PubMed1998

Chromosomal abnormalities in nodal and extranodal CD30+ anaplastic large cell lymphomas: infrequent detection of the t(2;5) in extranodal lymphomas.

To determine the significance of the t(2;5)(p23;q35) translocation in nodal and extranodal anaplastic large cell lymphoma (ALCL), we performed cytogenetic, molecular genetic, and immunohistochemical analyses of tumor tissues from 11 patients with CD30+ ALCL. Three of five patients with nodal ALCL had additional infiltration of the skin. Six patients had extranodal ALCL, two had primary intestinal ALCL, three had a primary cutaneous ALCL, and one had osseous ALCL. Cytogenetic investigation detected the t(2;5) in all patients with nodal ALCL but not extranodal ALCL. Tumor cells in t(2;5)+ lesions also stained immunohistochemically for p80NPM/ALK, whereas no staining for p80NPM/ALK was detected in extranodal ALCL. Two extranodal lesions had NPM/ALK fusion transcripts detected by nested reverse transcriptase-polymerase chain reaction. Fluorescence in situ hybridization analysis of these two lymphomas showed in one case a significant number (4%) of cells with a split hybridization signal, indicative of disruption of the NPM gene. Additional recurrent breakpoints observed in extranodal ALCL were 1p36, 6p25, and 8q24. Loss of genetic material occurred at 6q in one extranodal ALCL. Our results suggest that the t(2;5) more frequently plays a pathogenetic role in primary nodal than in extranodal ALCL and that this translocation may not be the primary event in some CD30+ ALCL.

Adult↗
PubMed1998

Trisomy 3 is not a common feature in malignant lymphomas of mucosa-associated lymphoid tissue type.

The genetic background of extranodal marginal zone B-cell non-Hodgkin's lymphoma (NHL) of mucosa-associated lymphoid tissue (MALT) type is poorly understood. In contrast to most entities of primary nodal lymphomas, few cytogenetic data are available, and gene rearrangements frequently encountered in and highly characteristic of certain entities of systemic NHL are absent in this type of lymphoma. Recently, it was suggested that MALT-type NHLs are associated with certain numerical chromosome aberrations and especially with trisomy 3. We performed an extensive study using a sensitive double (bicolor) fluorescence in situ hybridization technique for the analysis of trisomies for chromosomes 3, 7, 12, and 18 in 60 samples of low-grade and 45 high-grade MALT-type tumors. In the low-grade cases, trisomy 3 was found in a frequency of only 20%. High-grade lymphomas of MALT type were associated with trisomies 3, 7, 12, and 18 in 36, 20, 18, and 13% of the cases, respectively. Whereas no difference was encountered for trisomy 3 in primary and secondary/simultaneous high-grade lymphomas, +7 and +12 were associated with primary lymphomas, and a +18 was predominantly found in secondary/simultaneous high-grade NHL. These results challenge earlier reports describing a high frequency of +3 in low-grade MALT-type NHL and indicate a possibly different genetic evolution pattern of primary and secondary/simultaneous high-grade lymphomas of primary mucosal origin.

Cell Nucleus↗
PubMed1998

A comparison of biodegradable microparticles and MF59 as systemic adjuvants for recombinant gD from HSV-2.

A recombinant form of glycoprotein D from herpes simplex virus type-2 (gD2) was encapsulated into polylactide-co-glycolide (PLG) microparticles using a previously established solvent evaporation technique. The mean size of the microparticles was about 1 micron and high encapsulation efficiency of the antigen was achieved (70-80%). The microparticles were administered intramuscularly to Balb/C mice and the immune responses were compared with those obtained with the oil in water adjuvant MF59. The serum IgG response to gD2 induced by the microparticles was comparable with that induced by MF59. The serum neutralization titres were also comparable for microparticles and the emulsion. However, the microparticles induced a higher IgG2a isotype response and a more potent serum IFN-gamma response than MF59, suggesting a more Th1 type of response. The MF59 induced higher levels of serum IL-4 and IL-5 cytokines, suggesting a more Th2 type of response.

Adjuvants, Immunologic↗
PubMed1998

Inhibition of condensation in human chromosomes induced by the thymidine analogue 5-iododeoxyuridine.

Human lymphocyte cultures were treated with iododeoxyuridine. This 5-halogenated thymidine analogue induces distinct undercondensations of the heterochromatin of human chromosome 9. The condensation of the other heterochromatic regions on chromosomes 1, 15, 16 and Y is also inhibited, but to a lesser extent. Optimum cell culture conditions required for the induction of undercondensations were determined. Up to 90% of mitotic cells reveal chromosome 9 heterochromatin decondensations when the substance is present in quantities of 1 x 10(-4) M during the last 7 h before cell fixation. In addition, examples of the usefulness of 5-IUDR in the analysis of chromosome aberrations involving chromosome 9 are presented. The interaction between 5-IUDR and chromosomal DNA, the modification of chromosomal proteins and factors inducing chromosomal decondensations are discussed.

Cells, Cultured↗
PubMed1998

A lymphohistiocytic variant of anaplastic large cell lymphoma with demonstration of the t(2;5)(p23;q35) chromosome translocation.

Cytogenetic investigations were performed in a case of a nodal malignant non-Hodgkin's lymphoma. Histopathological analysis from an involved lymph node as well as from a skin biopsy revealed a lymphohistiocytic variant of CD30-positive anaplastic large cell lymphoma (ALCL). A t(2;5)(p23;q35) chromosome translocation could be observed in all metaphases analysed. This finding was confirmed both by RT-PCR analysis of the NPM/ALK fusion protein and by positive staining with the p80(NPM/ALK) antibody. To the best of our knowledge, this is the first report of a t(2;5) documented by classic cytogenetics in the lymphohistiocytic variant of ALCL.

Adult↗
PubMed1998

Abdominal T-cell non-Hodgkin's lymphoma of the gamma/delta type in a patient with selective immunoglobulin A deficiency.

A 28-year-old man presented with selective immunoglobulin A deficiency and severe diarrhea responding to a gliadin-free diet. Biopsy samples of the small intestine showed dense T-cell infiltrations in the lamina propria and a slight increase of intraepithelial T-lymphocytes. No clonal rearrangement of the T-cell receptor c-beta chain genes was detectable by Southern blotting. Four years later, at the age of 32, the patient was hospitalized again with liver failure, abdominal lymphadenopathy, pancytopenia, and recurrent bacterial infections. Retrospective polymerase chain reaction analysis of formalin-fixed tissues of the intestinal biopsy samples obtained 4 years earlier showed monoclonal T-cell receptor gamma-chain gene rearrangement. Lymphoid cells of the peripheral blood showed an immunophenotype of CD3-positive gamma/delta T cells with a negativity for CD4 and CD8. A clonally rearranged T-cell receptor delta chain gene and a germline configuration of the c-beta chain genes was found by Southern blotting. Cytogenetics showed an abnormal karyotype with unbalanced translocations t(1;5) and t(9;13). The patient died of extensive lung infiltrations by gamma/delta T cells; autopsy showed a peripheral T-cell lymphoma of the gamma/delta type in the enlarged abdominal lymph nodes. This is the first report of an abdominal T-cell lymphoma of the gamma/delta type in a patient with selective immunoglobulin A deficiency.

Abdominal Neoplasms↗
PubMed1998

Differential diagnosis between classic Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and paragranuloma by paraffin immunohistochemistry.

There are significant difficulties in the differential diagnosis of lymphomas at the interface between classic Hodgkin's lymphoma and both paragranuloma and T-cell-rich B-cell lymphoma as well as at the interface between T-cell-rich B-cell lymphoma and paragranuloma. We therefore investigated 197 cases (155 classic Hodgkin's lymphomas, 32 T-cell-rich B-cell lymphomas, and 10 paragranulomas) by paraffin immunohistochemistry. Special interest was given to cases with a B-cell phenotype of tumor cells. The reactive inflammatory infiltrate in both classic Hodgkin's lymphoma and T-cell-rich B-cell lymphoma was rich in TIA-1-positive cytolytic lymphocytes, and CD57-positive cells were rarely encountered. In contrast, in paragranuloma CD57-positive cells and small B-lymphocytes predominated the background infiltrate. The tumor cells in cases of classic Hodgkin's lymphoma were positive for CD30 in 95%, for CD15 in 75%, and for CD20 in 22%. Apart from this, vimentin was expressed in >95% of the cases. All cases of T-cell-rich B-cell lymphoma were negative for vimentin, CD30, and CD15. The reactivity of the tumor cells for CD30, CD15, CD20, and vimentin together with the background reactivity for CD57 and TIA-1 seem to reliably discriminate between the entities and should therefore help to increase the interobserver reproducibility of diagnoses in the gray zone around Hodgkin's lymphoma.

Antigens, CD20↗
PubMed1998

Lymphadenopathy: differentiation of benign from malignant disease--color Doppler US assessment of intranodal angioarchitecture.

PURPOSE: To differentiate reactive from malignant lymphadenopathy by using color Doppler ultrasonographic (US) findings of intranodal blood vessels. MATERIALS AND METHODS: Color Doppler US was performed in 117 lymph nodes in 100 consecutive patients before performance of surgical biopsy (47 nodes), neck dissection (62 nodes), or high-speed core biopsy (eight nodes). The presence of malignant changes in intranodal angioarchitecture (focal perfusion defects, aberrant course of central vessels, displacement of intranodal vessels, subcapsular vessels) was evaluated in each node. Inter- and intraobserver variability were evaluated. RESULTS: Histopathologic examination demonstrated 48 reactive lymph nodes (longest diameter +/- standard deviation, 13.5 mm +/- 6.0), 56 nodal metastases (longest diameter, 19.2 mm +/- 8.8), 12 malignant lymphomas (longest diameter, 23.2 mm +/- 10.5), and one node infiltrated by Langerhans cell histiocytosis. At color Doppler US, 103 (88%) nodes were classified correctly, with a specificity of 77% and a sensitivity of 96%. Reproducibility was 90%-96% (kappa = 0.79-0.91, P < .001). CONCLUSION: Color Doppler US is a reliable and reproducible method for help in the differentiation between reactive and malignant alterations of superficial lymph nodes by using findings of intranodal angioarchitecture.

Adolescent↗