Search PubMed⌕ Search

Biomedical subjects

M L Hansmann

Publications and source records attributed to M L Hansmann.

At least 73 records · Page 4Linked to original sources
PubMed1996

Molecular Ig gene analysis reveals that monocytoid B cell lymphoma is a malignancy of mature B cells carrying somatically mutated V region genes and suggests that rearrangement of the kappa-deleting element (resulting in deletion of the Ig kappa enhancers) abolishes somatic hypermutation in the human.

Five cases of monocytoid B cell lymphoma (MBCL) were analyzed for somatic mutations in the rearranged V region genes. Somatic mutations were found in four of the five cases, whereas one unusual CD5+ lymphoma harbored unmutated V region genes. Since somatic mutations are introduced into V region genes of antigen-activated B cells in the course of T cell-dependent immune responses, these results suggest a derivation of the tumor B cells in MBCL from antigen-experienced mature B cells. An analysis of the kappa-deleting element in two of the cases in which mutated VH but unmutated and nonfunctional V kappa gene rearrangements were found suggests that somatic hypermutation does not take place in human rearranged V kappa region genes when the C kappa gene and the kappa enhancers have been deleted in cis by rearrangement of the kappa-deleting element.

Amino Acid Sequence↗
PubMed1996

Pathology and "molecular histology' of Hodgkin's disease and the border to non-Hodgkin's lymphomas.

HD is characterized by a small amount of tumour cells (the H- and RS-cells) in a background of many, probably reactive, lymphocytes and histiocytes. Lymphocyte predominant HD seems to be a distinct clinicopathological entity of germinal centre cell origin and has a relatively favourable prognosis. This type has to be differentiated from mixed cellularity and nodular sclerosis HD, which show a different marker profile of the H- and RS-cells and their variants. Differentiation of progressively transformed germinal centres from lymphocyte predominant HD may be problematical and is based on the detection of L&H-cells in the latter entity. Diffuse paragranuloma may be difficult to differentiate from classic HD as well as non-Hodgkin's lymphomas, especially T-cell-rich B-cell lymphomas and peripheral T-cell lymphomas. In rare cases a distinction between HD and non-Hodgkin's lymphomas may be impossible. Similar to lymphocyte predominant HD, lymphocyte depletion HD may provide difficulties in its differential diagnosis from non-Hodgkin's lymphomas. The border with anaplastic large cell lymphoma cannot be clearly drawn and may be blurred. The border between HD and non-Hodgkin lymphomas may be especially blurred in composite lymphomas, if single cell studies can demonstrate a common clonal origin of both parts of the lymphoma. Analysis of immunoglobulin or T-cell receptor variable region genes amplified by PCR from single cells picked from histological sections ("molecular histology') combines morphological characterization and identification of H- and RS-cells with a molecular analysis of those cells. This enables one not only to determine the nature of H- and RS-cells and their clonality but also to answer questions about the relationship between Hodgkin and non-Hodgkin's lymphomas.

Diagnosis, Differential↗
PubMed1996

Single cell analysis of Hodgkin/Reed-Sternberg cells.

The origin and clonality of the Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) has been much debated. Recently, single cell PCR techniques were established, allowing the study of HRS cells at the single cell level. HRS cells were analysed for Ig gene rearrangements to reveal a potential origin from B lineage cells. Whereas one study did not detect any V gene rearrangements, such rearrangements were found in three other investigations. However, whereas our own group detected clonal V gene rearrangements in the HRS cells of 11 (10 classical and one lymphocyte predominant) out of 12 cases of HD and no rearrangements in the twelfth, Delabie et al. (Blood 1994; 84: 3291-8) described four cases of lymphocyte predominant HD with polyclonal V gene rearrangements and Hummel and colleagues detected monoclonal as well as polyclonal and "mixed' populations of HRS cells in cases of classical HD. Potential reasons for the differing results of those investigations are discussed.

Animals↗
PubMed1996

Lymphocyte predominant Hodgkin's disease--a workshop report. European Task Force on Lymphoma.

Since lymphocyte predominant Hodgkin's disease (LPHD) may comprise more than one entity, diagnostic criteria, clinical features, and treatment strategies are still being controversially discussed. Thus, in December 1994 a multinational project on lymphocyte predominant Hodgkin's disease was initiated by the European Task Force on Lymphoma. This project is aimed at clarifying the clinical and histopathological spectrum of LPHD, as well as its relation to T-cell- rich B-cell lymphoma and classical types of HD. 525 paraffin blocks and clinical data of 478 patients from 16 international centres were submitted. At the Third International Symposium on Hodgkin's Lymphoma in Cologne, 232 of these cases were discussed by an expert panel. The preliminary results are presented here. Most cases of LPHD were reclassified into nodular paragranuloma (NP) and lymphocyte rich classical HD. In both groups, a considerable number of cases with atypical features was observed. Few cases of NHL were found among the cohort. LPHD was generally treated according to common standards for HD. The whole group of LPHD did not have a better prognosis than NS; whereas early stage NP did perform better than early stage NS (data from the German Hodgkin's Lymphoma Study Group). There is however a striking discrepancy between good survival and the frequent relapses observed in NP which needs to be elucidated.

Hodgkin Disease↗
PubMed1996

Single-cell analysis of T-cell receptor-gamma rearrangements in large-cell anaplastic lymphoma.

Large-cell anaplastic lymphomas (LCAL) are characterized by their distinctive morphology together with expression of the CD30 antigen. In addition, a chromosomal translocation, t(2;5) (p23; q35), can be detected in most cases. A significant proportion of LCALs carry rearrangements of the T-cell receptor-gamma (TCR-gamma) locus and display a T-cell phenotype. In about a third of the cases, another type of non-Hodgkin-lymphoma precedes LCAL. Early transformations of non-Hodgkin's lymphoma into LCAL might escape clinical detection in a significant number of cases. The existence of clonally related lymphoid cells within the lymph node infiltrates must be claimed in these cases. Recently, a small-cell-predominant variant of LCAL was described in which only few large tumor cells expressing the CD30 antigen are found together with numerous small lymphocytes, which are frequently CD30-. This observation in particular prompted us to investigate the clonal relationship of the tumor cell compartment and admixed small lymphocytes in one case of common LCAL with T-cell genotype. For this purpose, we chose to amplify rearranged TCR-gamma sequences from single cells isolated from immunostained frozen sections by using a micromanipulator. A total of 119 cells were investigated. Amplification products were obtained in 17 of 79 CD3+ cells, 12 of 30 CD30+ cells, and three of 10 CD20+ cells. The nucleotide sequences were determined in 28 cells by nonradioactive sequencing. In 11 CD30+ cells, the predominant rearrangement of TCR-gamma was identified. No clonal diversity was observed. The small CD3+ lymphocytes were unrelated to the anaplastic CD30+ tumor cells. This report describes a method to analyze rearrangements of the TCR-gamma in single cells isolated from immunostained frozen sections. Application of this technique revealed an absence of clonal diversity in a case of LCAL and documented the polyclonal nature of admixed small CD3+ lymphocytes.

Cell Separation↗
PubMed1996

Nasal T/NK cell lymphoma: a clinico pathologic study of 30 west Chinese patients with special reference to proliferation and apoptosis.

Midfacial T-cell lymphomas are more prevalent in Asia than in Europe or North America. Clinically, these lymphomas are noted as one major differential diagnosis in the malignant midline granuloma syndrome. During the past years, the group of nasal T/NK cell lymphomas has been recognized that is frequently associated with EBV-infection. The aim of the current publication was to describe the clinical presentation and course of 30 patients attending the West China University of Medical Sciences, Chengdu, P.R. China, between 1991 and 1994. Clinical records were assessed and the patients were followed for 6 to 29 (mean 12.4) months. Several microscopic features thought to be associated with this entity were carefully evaluated together with immunohistochemical data. The proliferation of the tumour cells was assessed by determining the mitotic index and the ratio of MIB-1 labelled cells. In addition, the incidence of apoptotic cells was investigated by means of the in-situ end labelling (ISEL) technique. Our data confirm the expression of T-cell markers by T/NK cell lymphomas as determined by the immunohistochemistry. The apoptotic index was found to correlate with the ratio of MIB-1 labelled cells. Expression of the bcl-2 oncoprotein was not associated with increased or diminished proliferation or cell death, respectively. Eight of the thirty patients succumbed to their disease during the follow-up period. Kaplan-Meier cumulative survivals and log-rank tests revealed a significant impact of MIB-1 labelling on mean survival times.

Adolescent↗
PubMed1996

Differential diagnosis of L26-positive, CD15-negative Hodgkin's disease and large B-cell lymphoma with a high content of reactive T-cells: a morphologic and immunohistochemical study.

B-cell non-Hodgkin's lymphomas with a marked preponderance of reactive T cells, so-called T-cell rich B-cell lymphomas (TCRBCLs), can be morphologically confused with Hodgkin's disease (HD). To establish helpful distinguishing features in paraffin sections, 10 cases of L26-positive, CD15-negative HD and 10 cases of TCRBCL were compared; 4 cases of HD had morphologic features of the nodular lymphocyte predominant (LP) type. Nine of 10 cases of HD contained fewer than 20 mitoses/20 high power fields (hpf) and only 1 had pericapsular involvement. In contrast, 9 of 10 TCRBCL had greater than 20 mitoses/20 hpf and 7 had perinodal infiltration. HDLP was easily distinguished from TCRBCL by the expanded dendritic meshworks outlining the L & H nodules and the high content of CD57-positive lymphocytes. The remaining 6 cases of non-LP L26-positive HD had a relatively distinctive immunostaining pattern, with absence of CD45 and discordant reactivity for L26 and Ki-B5 in Reed-Sternberg cells and variants. Only 3 cases of TCRBCL had a similar CD45 and L26/Ki-B5 immunostaining pattern, and these could be distinguished by demonstrable cytoplasmic light-chain restriction. These results show that evaluation of the mitotic count, pericapsular involvement, and immunohistochemical staining patterns for Ki-M4p, CD57, L26/Ki-B5, and CD45 can help to discriminate TCRBCL from L26-positive HD when only fixed material is available.

Adult↗
PubMed1996

[A comparative study of apoptosis and proliferation of nasal T cell lymphoma].

A quantitative evaluation and statistical analysis of apoptosis and proliferation in 30 cases of MMR was carried out by means of in situ end-labelling (ISEL) of fragmented DNA technic and expression of Ki-67 antigen in routine paraffin sections with comparison of clinicopathology and prognosis. 28 patients had been followed for 6 to 29 months (mean 12.4 months) and 8 (28.5%) died of relapse and idsease progression. The results showed that (1) the number of apoptotic cells was found to correlate with the ratio of Ki-67 positive cells (P < 0.0063). No significant association of mitotic figures, Ki-67 labelled cells and the expression of bel-2 oncoprotein was observed. The results also did not suggest a correlation of proliferation or apoptosis with the stage of the disease at presentation. (2) statistical analysis revealed a significant impact of Ki-67 positive cells (P < 0.0160) on mean survival time and no significant association among apoptosis, morphologic changes and the mean survival time was found in this group of cases. The relation between apoptosis, proliferation, expression of bcl-2 oncoprotein and EBV infection in related lymphomas were discussed.

Adult↗
PubMed1995

Secretion of cytokines (interleukins-1 alpha, -3, and -6 and granulocyte-macrophage colony-stimulating factor) by normal human bone marrow megakaryocytes.

The effects of cytokine stimulation [recombinant human interleukin (rhIL)-1 alpha, rhIL-3, rhIL-6, rhIL-11, and rh granulocyte-macrophage colony-stimulating factor (GM-CSF)] on the secretory activity of normal human megakaryocytes were studied by means of the reverse hemolytic plaque assay (RHPA) in enriched cell preparations. This test facilitates an extremely sensitive determination of cytokine secretion at the single-cell level, together with the clear-cut identification of each immunostained (CD61) secretory active megakaryocyte. Moreover, the reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the expression of IL-6, IL-6 receptor (IL-6R), IL-9, IL-10, IL-12, and IL-13 mRNA in highly concentrated megakaryocyte preparations. In comparison with the spontaneous secretion rate, stimulation with rhIL-1 alpha, rhIL-6, and rhGM-CSF failed to induce a significant increase in the release of cytokines by CD61+ cells. On the other hand, both rhIL-3 and, in a less pronounced way, rhIL-11 exerted a marked effect on IL-6 secretion. Additionally, after stimulation with rhIL-3, a significant enhancement of the secretion of IL-3 and GM-CSF, but not of IL-1 alpha, could be observed. Using the RT-PCR, a significant induction of IL-6 expression could be appreciated in the enriched megakaryocyte population (60% to 80%) stimulated with rhIL-3. The results of this study provide persuasive evidence that a number of cytokines are synthesized and secreted by human megakaryocytes and not only by hematopoietic stroma cells. These data suggest the existence of autocrine and paracrine mechanisms that may influence maturation and differentiation of megakaryocytes as well as act on various stroma cells to sustain an appropriate hematopoietic micro-environment.

Base Sequence↗
PubMed1995

[Hodgkin cells are clonal B-cells in various stages of differentiation].

Hodgkin's disease, especially its biology and pathogenesis, has been under discussion for more than 160 years. Numerous investigations have focused on the nature and clonality of Hodgkin cells, but so far no definitive answer have been yielded by immunohistochemistry, Southern blotting and PCR. However, the use of single-cell PCR has now made it possible to answer the question of the derivation of Hodgkin cells. Using a micromanipulator, Hodgkin cells can be picked out of histological sections and B-cell specific gene rearrangements (VDJ) can be amplified. With this technique it has proved possible to demonstrate the B-cell derivation of Hodgkin cells and their clonality. Mutated immunoglobulin genes in lymphocyte-predominant Hodgkin's disease indicate a germinal center cell origin of Hodgkin cells of this type. These findings, however, do not exclude cases of Hodgkin's disease with Hodgkin cells with a T-cell genotype.

Antigens, CD↗
PubMed1995

[Apoptosis in Hodgkin's disease].

Previous studies have concentrated on the proliferative behaviour of the neoplastic cell compartment in Hodgkin's disease (HD). The aim of the current investigation was to analyse the frequency of programmed cell deaths in Hodgkin and Reed-Sternberg (HRS) cells in the different subtypes of HD and to correlate this phenomenon with the expression of the bcl-2 oncogene. For this purpose, we investigated paraffin-embedded material from 63 cases of HD. Oncogene expression was determined by immunohistochemistry with the monoclonal antibody bcl-2-124. The detection of apoptotic cells was facilitated by application of the in situ end-labelling (ISEL) technique. Our results confirmed that bcl-2 expression is low in the lymphocyte-predominant subtype of HD. Apoptotic cells were found in all subtypes to a variable extent and were not significantly associated with any particular subtype. Interestingly, there was no correlation of bcl-2 expression and the presence or absence of apoptotic HRS cells. Hence, other factors must be operative in the regulation of programmed cell death in HD. Such mechanisms have been described for lymphocytes under various conditions, such as negative selection in germinal centres and within the thymus, DNA damage due to irradiation, and cellular cytotoxicity.

Apoptosis↗
PubMed1995

[Extraneural metastasis of brain and spinal cord tumors. Report of 2 cases].

This case report refers to two patients with the rare entity of an extraneural metastasizing central nervous system tumor. The first patient presented with ipsilateral cervical lymph node metastases 4 years after a diagnostic biopsy and 2 years after removal of an anaplastic oligodendroglioma, respectively. The origin of the metastases was confirmed by immunohistochemistry. The second case described was found in a 26-year-old female who had suffered from a spinal cord pilocytic astrocytoma in infancy and been treated by surgery and radiotherapy. On postmortem examination, transformation to a primitive neuroectodermal tumor was found. Morphological and immunohistochemical features of the metastases were exactly identical with those of the primary tumors in both cases. The pathomechanisms of metastasizing CNS tumors are discussed with reference to the reasons why such cases are so rarely observed. The incidence of remote metastases and differences depending on tumor type are estimated. No relation to malignancy grade can be detected.

Adolescent↗
PubMed1995

Molecular single-cell analysis of Hodgkin and Reed-Sternberg cells.

In Hodgkin's disease, the malignant Hodgkin and Reed-Sternberg (HRS) cells are present in very small numbers in the diseased tissue, thus making molecular analysis of these cells very difficult. Using micromanipulation and single-cell polymerase chain reaction (PCR), rearranged immunoglobulin genes can be amplified and sequenced from single HRS cells. Oligonucleotides chosen from the variable (V)-gene sequences identified in the HRS cells can be used as specific markers for the tumour clone. This technique will allow one to search for members of the tumour clone in various compartments of the patient's body, to follow disease progression during therapy, and to analyse stem-cell populations for contamination by tumour cells before autologous bone-marrow transplantation.

Animals↗
PubMed1995

Monocytoid B-cell reaction associated with peripheral T-cell lymphomas.

Benign monocytoid B-cells (MBCs) proliferation was reported to occur in various lymphoproliferative disorders, but not in peripheral T-cell lymphomas (PTCL). In our review of fifty three nodal-based, low and high grade PTCL, MBCs were identified histologically and immunohistochemically in eight of the cases. They included: chronic lymphocytic leukaemia of T-cell type (n = 1) with multiple MBCs clusters, large cell anaplastic lymphoma (n = 1) showing lymphoma cells within multiple MBCs foci, and PTCL of angioimmunoblastic lymphadenopathy (AILD) type (n = 6) with solitary (n = 4) or multifocal (n = 2) MBCs reaction. Progression from AILD-hyperimmune reaction to PTCL of AILD type could be observed in one case by three consecutive follow-up biopsies. While MBCs proliferation associated with hyperimmune reaction was prominent, in PTCL of AILD type only isolated or small multiple clusters of MBCs were present. In PTCL of AILD type, MBCs seemed to be a residual component of a prior hyperimmune reaction diminishing with progress of the disease. Therefore we assume that the development of PTCL of AILD type from preceding hyperimmune reaction is more common than previously considered. Cytologically, MBCs proliferation associated with PTCL shows two cell types, as described in reactive lymphadenopathies: the common type and the large cell type MBCs.

Adult↗
PubMed1995

Reactive versus neoplastic monocytoid B-cell proliferations. In situ hybridization study of immunoglobulin light chain mRNA.

To distinguish reactive versus neoplastic monocytoid B-cell (MBC) proliferations, the clonality of MBC was examined in paraffin-embedded tissues by in situ hybridization (ISH) of immunoglobulin (Ig) light chain messenger RNA (mRNA) with sensitive oligonucleotide probes in 26 cases. They included 13 cases of lymphadenitis with MBC reaction and 13 cases of nodal (n = 8) and extranodal (n = 5) monocytoid B-cell lymphoma (MBCL). Two cases represented a composite lymphoma showing a centroblastic-centrocytic and MBCL component. The clonality of MBC infiltrates could be demonstrated in 16 of 26 (61.5%) cases by immunostaining for Ig light chains and in all (100%) cases by ISH. Neoplastic MBC usually expressed a faint-to-moderate light chain restriction of mRNA, whereas some MBC (10% to 30% of total MBCL population) showed a strong positivity irrespective of plasmacytoid differentiation as indicated by Ig immunostaining (present in 9 of 13 cases). Reactive MBC expressed a faint kappa and lambda light-chain mRNA positivity. Five percent to 20% of total reactive MBC showed also a strong positivity for both Ig light chain mRNA, although only a minor part of these cells (7 of 13 cases) expressed polyclonal Ig by immunohistochemistry. These results indicate that (1) both reactive and neoplastic MBC can differentiate into plasma cells; and (2) a relatively high percentage of reactive and neoplastic MBC show a detectable mRNA transcription, but not a corresponding Ig synthesis. Either the Ig detection is not sensitive enough or these cells might be in an early differentiation phase, where the Ig production has not yet started.

Adolescent↗
PubMed1995

Combination of Hodgkin's disease and diffuse large cell lymphoma: an in situ hybridization study for immunoglobulin light chain messenger RNA.

It is not clear whether the rare combination of Hodgkin's diseases with non-Hodgkin lymphomas are true composite lymphomas or differentiation stages of one tumour cell clone. We used in situ hybridization and immunohistochemistry for the demonstration of immunoglobulin light chains in order to investigate the relationship between the two lymphoma components. In three cases of nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma the Hodgkin cells, as well as the tumour cells in the diffuse large B-cell lymphoma, showed the same messenger RNA for one light chain. Thus, using in situ hybridization in nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma in a small number of cases a possible genetic relationship between the two components could be shown. In nodular sclerosis combined with diffuse large B-cell lymphoma, in situ hybridization did not support a common clonal origin of both tumour parts. However, a unique clonal derivation cannot be excluded by the techniques applied.

Hodgkin Disease↗
PubMed1995

CD34+ human hemopoietic progenitor cells of the bone marrow differ from those of the peripheral blood: an immunocytochemical and morphometric study.

CD34+ progenitor cells were harvested from bone marrow and peripheral blood from 10 healthy donors by immunomagnetic isolation and enrichment procedures. The CD34+ cell population was investigated using a battery of enzyme reactions and monoclonal antibodies on cytospin preparations. Additionally, morphometric measurements were carried out and also liquid suspension culture studies were performed to ascertain vitality and stem cell character. More than 95% of the total yield of medullary CD34 progenitors expressed CD45 (LCA), CD43 (MT1) and beta-glucuronidase. Reactivity with CD33 (My9), CD15 (LeuM1), CD38 (Leu17), CD20 (L26) and Ret40f (glycophorin C) was assumed to be in keeping with a transition into more differentiated elements of the various hemopoietic lineages. Morphometric analysis revealed conspicuous heterogeneity of the CD34+ cell population considering size measurements. This finding was in line with the diversities of antigen expression, indicating the more committed nature of CD34+ stem cells derived from the bone marrow in comparison with those progenitors isolated from the peripheral blood. Moreover, proliferation marker staining by PCNA disclosed a positivity in a considerable number of progenitors in contrast to the findings in CD34+ cells that are found in the peripheral blood.

Antibodies, Monoclonal↗