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Biomedical subjects

G Ott

Publications and source records attributed to G Ott.

At least 19 recordsLinked to original sources
PubMed2007

[Extranodal diffuse large B-cell lymphoma--an organotypic disease?].

Roughly 30-40% of diffuse large B-cell lymphomas (DLBCL) arise primarily in extranodal sites. Most frequently, they occur in the gastrointestinal tract, especially in the gastric mucosa. They also occur in the central nervous system, as testicular lymphomas, in the lungs, or in the skin. Morphologically, they show the whole spectrum of peripheral B-blasts: centroblasts, immunoblasts, or plasmoblasts. Thus, there is no actual difference in their cytomorphological presentation compared to their nodal-and frequently systemic-counterparts. However, recent data point to profound differences in primary extranodal DLBCL compared to primary nodal tumors, as well as to each other, frequently relating to their molecular characteristics and especially implying organotypic features. These characteristics may relate to a particular organotypic site of origin, or the particular clinico-pathogenetic setting in which the tumors arise. This is exemplified in the description of the DLBCL subtypes as defined by the World Health Organization classification (mediastinal or intravascular B-cell lymphoma; primary effusion lymphoma). On the other hand, primary extranodal DLBCL are frequently characterized by a particular (cyto-)genetic constitution, often related to their site of origin. Finally, some preliminary data on gene expression profiling strongly argue in favor of particular gene signatures for primary extranodal DLBCL, and hence in favor of particular organotypic transformation pathways.

Central Nervous System Neoplasms↗
PubMed2007

[Extranodal marginal zone B-cell lymphoma of MALT-type].

Extranodal marginal zone B-cell lymphomas of the MALT type constitute, with around 8% of all B-cell lymphomas, the third most frequent lymphoma in the Western hemisphere. Their unifying characteristic principle is their origin in organs that are typically devoid of a regular lymphatic parenchyma ("primary" MALT). In contrast, "secondary" MALT is acquired in these sites by chronic inflammatory processes triggered by chronic infections or autoimmune diseases. The organotypic characteristics of these particular lymphoid tumours are also mirrored by organ-specific precursor lesions and in tumour biology. Usually, MALT-type lymphomas remain confined to their site of origin for a long time, disseminating only late during the course of the disease. Hence, they may be controlled by local treatment (excision, irradiation). Moreover, the distinctive genetic constitution of MALT-type lymphomas, although varying from organ to organ, indicates particular transformation pathways obviously related to the specific precursor lesion and, hence, of organ-specific quality.

Autoimmune Diseases↗
PubMed2006

[DNA-chips in the diagnosis of hematological malignancies].

In hematological malignancies, gene expression profiling using DNA-microarrays led to the discovery of novel lymphoma and leukemia subgroups. The heterogeneous entity of diffuse large B-cell lymphoma could be subdivided into the germinal center B-cell-like and the activated B-cell-like subtype which differ in pathogenesis and clinical behavior. In leukemia, existing entities defined by morphological, cytogenetic, molecular and immunophenotypic criteria were confirmed on the global gene expression level; in addition, new important molecular subgroups could be identified. In retrospective clinical lymphoma and leukemia studies, robust gene expression signatures were discovered that predict the clinical course at the time of diagnosis. Given the huge potential of the DNA-microarray technology, application in the routine diagnostic setting appears possible.

Biomarkers, Tumor↗
PubMed2006

Characterization of chromosomal aberrations in diffuse large B-cell lymphoma (DLBL) by G-banding and spectral karyotyping (SKY).

Cytogenetic chromosome analysis by classical G-banding was supplemented by spectral karyotyping (SKY) in 12 cases of diffuse large B-cell lymphoma (DLBL). SKY is a fluorescence in-situ-based, genome-wide screening technique allowing identification of genetic material even in highly condensed metaphase chromosomes of poor morphology. By simultaneous hybridization of whole chromosome painting probes onto tumor chromosome spreads genetic rearrangements are visualized permitting the clarification of even complex karyotype alterations and the identification of genetic material of previously unknown origin, so-called marker chromosomes. Taking the SKY results into account, we reevaluated the G-banding karyotypes initially carried out, thus generating a more precise karyotype in ten of twelve (83%) cases investigated. In particular, thirteen chromosomal rearrangements not correctly recognized by classical cytogenetics were identified, the genetic origin of seven marker chromosomes was elucidated and three structural genetic rearrangements were redefined. We found SKY to be a valuable technique to establish a definite karyotype in addition to classical cytogenetics.

Chromosome Aberrations↗
PubMed2005

[Mediastinal large B-cell lymphoma with symptomatic superior vena cava syndrome in a patient with bichorial twin pregnancy in the 26th week of gestation: peri-and postpartal management -- a case report].

OBJECTIVE: Non-Hodgkin lymphoma (NHL) is rarely observed during pregnancy. The clinical behavior of this malignancy does not differ significantly from that outside of the setting of pregnancy. Antineoplastic chemotherapy is usually given during the second and third trimester. However, irradiation is another therapeutic option. The teratogenic potential limits its use in pregnancy. Finding an appropriate therapeutic management in an emergency setting is therefore difficult. CASE REPORT: In this report, we describe the case of a 31-year-old gravida three, para two, in whom a mediastinal large B-cell lymphoma with symptomatic superior vena cava syndrome was diagnosed in a bichorial twin pregnancy in the 26 (th) week of gestation. After premature delivery by caesarean section at 26 + 0 weeks gestation the patient was immediately submitted to mediastinal irradiation. The clinical symptoms resolved and adjuvant CHOEP-chemotherapy was instituted. Chemotherapy was well tolerated and a partial remission was observed after 4 cycles. The neonatological follow-up was uneventful. DISCUSSION: To our knowledge, this is the first case in the literature of a patient with bichorial twin pregnancy with large cell mediastinal NHL and symptomatic superior vena cava syndrome who underwent irradiation after caesarean section because of life-threatening medical condition.

Adult↗
PubMed2005

Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases.

AIMS: Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology. METHODS AND RESULTS: Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL. CONCLUSIONS: MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.

Aged↗
PubMed2004

Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome.

To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138+/-, bcl-6-, corresponding to an activated B-cell phenotype. Immunoglobulin-V(H) gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.

Adult↗
PubMed2004

[The spectrum of lymphoproliferations and malignant lymphoma after organ transplant].

Lymphoproliferative disease in patients with organ transplantation has increasingly been diagnosed in recent years. It is caused by immunosuppression after organ transplantion. A large percentage of these tumors is associated with Epstein-Barr virus infection. The classification differentiates between early lesions, polymorphic and monomorphic lymphoproliferations. Whereas the early lesions are often polyclonal, the remaining groups are mostly monoclonal. Polymorphic lymphoproliferative disease shows a wide spectrum of B-cell differentiation, whereas monomorphic proliferations resemble sproadic malignant lymphomas. The latter also show genetic abberations of the c-myc-, Ras-, p53- and Bcl6-genes. With reference to the germinal center reaction, posttransplant lymphoproliferations have to be assigned to the post-follicular activated B-cell type. While until 1991 only 2% of the cases of PTLD had an EBV-association, the EBV-associated PTLD have been frequently observed in recent times and presently constitute about 20% of the cases. EBV-negative PTLD constitute a negative prognostic factor. Posttransplant lymphomas might also represent a model for sporadic lymphoproliferative disease, that for example also occurs at elderly patients.

B-Lymphocytes↗
PubMed2003

Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma.

Recently, centrosome aberrations have been described as a possible cause of aneuploidy in many solid tumors. To investigate whether centrosome aberrations occur in non-Hodgkin's lymphoma (NHL) and correlate with histologic subtype, karyotype, and other biological disease features, we examined 24 follicular lymphomas (FL), 18 diffuse large-B-cell lymphomas (DLCL), 33 mantle cell lymphomas (MCL), and 17 extranodal marginal zone B-cell lymphomas (MZBCL), using antibodies to centrosomal proteins. All 92 NHL displayed numerical and structural centrosome aberrations as compared to nonmalignant lymphoid tissue. Centrosome abnormalities were detectable in 32.3% of the cells in NHL, but in only 5.5% of lymphoid cells from 30 control individuals (P<0.0001). Indolent FL and MZBCL contained only 25.8 and 28.8% cells with abnormal centrosomes. In contrast, aggressive DLCL and MCL harbored centrosome aberrations in 41.8 and 35.0% of the cells, respectively (P<0.0001). Centrosomal aberrations correlated to lymphoma grade, mitotic, and proliferation indices, but not to the p53 labeling index. Importantly, diploid MCL contained 31.2% cells with abnormal centrosomes, while tetraploid samples harbored centrosome aberrations in 55.6% of the cells (P<0.0001). These results indicate that centrosome defects are common in NHL and suggest that they may contribute to the acquisition of chromosomal instability typically seen in NHL.

Cell Division↗
PubMed2003

Immunohistochemical analysis of B-cell lymphoma using tissue microarrays identifies particular phenotypic profiles of B-cell lymphomas.

AIMS: To validate the applicability of tissue microarray (TM) in immunohistochemical profiling of B-cell lymphoma and to identify particular phenotypic profiles of B-cell neoplasms. METHODS AND RESULTS: Eighty-two diffuse large B-cell lymphomas (DLBL), 54 follicular lymphomas (FL) and 74 mantle cell lymphomas (MCL) were arrayed. Immunohistochemical stains of TM were compared with immunostains of conventional, formalin-fixed and frozen material sections. Concordant staining results were obtained in more than 88% of cases for CD20, CD3, CD5, CD10, CD23, Bcl-2, IgD, secretory differentiation, p53 and p21 expression. Prognostically relevant hot-spot expression of Ki67 yielded concordant results in 71%. Applying TM for characterization of p27KIP1 expression, both typical and blastoid MCL only rarely showed p27KIP1 expression (9% and 15%), whereas 32% of nodal DLBL were p27KIP1-positive, irrespective of high proliferative activity. Among 22 B-cell lymphomas investigated genetically, a p53 + p21- immunophenotype in >20% of tumour cells correlated with p53 locus deletion. CONCLUSIONS: Lymphoma TM allows for immunohistochemical profiling of human B-cell lymphoma with a comparable accuracy to immunohistochemical studies performed on conventional tissue sections. Nodal DLBLs showed significantly more frequent expression of IgD and p27KIP1 than extranodal DLBL. MCL and DLBL frequently showed aberrant p27KIP1 expression. A p53 + p21- immunophenotype in >20% of tumour cells in B-cell non-Hodgkin's lymphoma correlates with p53 gene deletion.

Biomarkers, Tumor↗
PubMed2002

Synergistic adjuvant activity of immunostimulatory DNA and oil/water emulsions for immunization with HIV p55 gag antigen.

A synthetic oligonucleotide containing a previously identified adjuvant active CpG DNA sequence was evaluated for its ability to augment antibody and CTL responses to p55 gag from HIV-1 in mice. Surprisingly, the CpG oligonucleotide, although, it had previously been described as the most potent adjuvant sequence in mice for the particulate HbsAg, was ineffective when used in a simple combination with urea-solubilized p55 antigen. However, a potent adjuvant effect was observed with the CpG sequence when it was formulated with emulsions. Enhancement of antibody titer by CpG emulsion formulations was observed with urea-solubilized p55 antigen, however, significantly higher titers were obtained with p55 bound to polylactide-co-glycolide microparticles. In both cases IgG2a was enhanced in the presence of CpG. It appears likely that presentation of CpG with emulsions and particulate antigens enhances their delivery into antigen presenting cells (APC) and results in more effective presentation of antigen and adjuvant. To support this hypothesis, preliminary in vitro studies were undertaken to show upregulation of CD86 on mouse bone marrow-derived dendritic cells (BMDC) in vitro, following incubation with CpG formulations.

AIDS Vaccines↗
PubMed2002

[Myelosarcoma of the proximal jejunum. A rare primary condition of acute myelogenous leukemia].

Myelosarcoma (chloroma) is a rare primary condition in patients with either a myelodysplastic syndrome, or an acute or chronic leukemia. It is an extramedullary neoplasm which does not commonly present with changes in peripheral blood or bone marrow. The rarity and histomorphological similarity to malignant non-Hodgkin lymphoma renders the diagnosis notoriously difficult. Due to its coincidental or secondary manifestation followed by myelogenous leukemia, this tumor needs to be seen as a primary systemic disease. We present a 40 year old man with myelosarcoma of the jejunum and discuss this entity and its therapeutic options.

Adult↗
PubMed2002

[Molecular diagnosis in hematopathology].

The diagnosis of hematopoietic neoplasias has nowadays become more and more refined by molecular cytogenetic and molecular biological techniques. The biological basis of most of these techniques is that (malignant) tumors represent clonal neoplasias that are derived from a single or few progenitor cells, thus imparting a clonal relationship to all daughter cells. Apart from clonality analysis as a marker for neoplastic growth, the presence or absence of certain primary chromosome abnormalities, and the number and the kind of secondary genetic anomalies become increasingly important in the delineation of the biological grade of aggressiveness.

Biomarkers, Tumor↗
PubMed2002

Tyrosine phosphorylation in human lymphomas.

In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated whether oncogenic tyrosine kinase activation also occurs in other categories of lymphoma by staining 145 cases of lymphoma covering those tumours with a range of different subtypes including those with morphological similarity to ALK-positive anaplastic large cell lymphoma (ALCL). Twelve cases of the borderline malignant disorder lymphomatoid papulosis were also studied. Twenty seven of the 28 cases of ALK-positive ALCL showed the extensive cytoplasmic labelling for phosphotyrosine in the neoplastic cells. The remaining case containing moesin-ALK exhibited membrane-associated phosphotyrosine expression. There was no nuclear phosphotyrosine labelling in any of the ALK-positive ALCL, even though ALK was present within the cell nuclei in 23 of the tumours. Variable degrees of phosphotyrosine labelling, usually membrane-restricted, were observed in 7/40 cases of ALK-negative ALCL, 9/29 cases of diffuse large B-cell lymphoma, 3/6 cases of mediastinal B-cell lymphoma, 2/7 cases of Hodgkin's lymphoma, 3/6 cases of peripheral T-cell lymphomas unspecified, 4/6 cases of B-cell chronic lymphocytic leukaemia, 2/6 cases of follicular lymphomas and 2/12 cases of lymphomatoid papulosis studied. However none of these phosphotyrosine-positive cases showed the strong cytoplasmic labelling comparable to that seen in ALK-positive lymphoma. We conclude that activation of a tyrosine kinase is probably not a major oncogenic event in lymphomas other than ALK-positive ALCL.

Cell Nucleus↗
PubMed2002

The extracellular regulated kinases (ERK) 1/2 mediate cannabinoid-induced inhibition of gap junctional communication in endothelial cells.

1. Cannabinoids are potent inhibitors of endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations. We set out to study the mechanism underlying this effect and the possible role of cannabinoid-induced changes in intercellular gap junction communication. 2. In cultured endothelial cells, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the cannabinoid receptor agonist HU210, increased the phosphorylation of extracellular regulated kinases 1/2 (ERK1/2) and inhibited gap junctional communication, as determined by Lucifer Yellow dye transfer and electrical capacity measurements. 3. Delta(9)-THC elicited a pronounced increase in the phosphorylation of connexin 43, which was sensitive to PD98059 and U0126, two inhibitors of ERK1/2 activation. Inhibition of ERK1/2 also prevented the Delta(9)-THC-induced inhibition of gap junctional communication. 4. Delta(9)-THC prevented both the bradykinin-induced hyperpolarization and the nitric oxide and prostacyclin-independent relaxation of pre-contracted rings of porcine coronary artery. These effects were prevented by PD98059 as well as U0126. 5. In the absence of Delta(9)-THC, neither PD98059 nor U0126 affected the NO-mediated relaxation of coronary artery rings but both substances induced a leftward shift in the concentration - relaxation curve to bradykinin when diclofenac and N(omega)nitro-L-arginine were present. Moreover, PD98059 and U0126 prolonged the bradykinin-induced hyperpolarization of porcine coronary arteries, without affecting the magnitude of the response. 6. These results indicate that the cannabinoid-induced activation of ERK1/2, which leads to the phosphorylation of connexin 43 and inhibition of gap junctional communication, may partially account for the Delta(9)-THC-induced inhibition of EDHF-mediated relaxation. Moreover, the activation of ERK1/2 by endothelial cell agonists such as bradykinin, appears to exert a negative feedback inhibition on EDHF-mediated responses.

Animals↗
PubMed2001

[Enteropathy-associated T-cell lymphoma. Manifestation as diet-refractory coeliac disease and ulcerating jejunitis].

HISTORY AND CLINICAL FINDINGS: A 61-year-old woman in poor general health was admitted to hospital because of progressive diarrheo, flatulence, fatigue and weight loss. The patient had a history of coeliac disease with poor dietary compliance over many years. Hence, the present clinical deterioration was unresponsive to a gluten-free diet. INVESTIGATIONS: Laboratory results showed signs of inflammation and malabsorption. The endoscopy of the duodenum revealed a flattened mucosal architecture, as is typical for coeliac disease. Enteroscopy revealed many small jejunal lesions. Histological examination of mucosa showed typical signs of coeliac disease without definite signs of lymphoma. Immunhistochemical analysis showed atypical intraepithelial T-cells, while the molecular biological study revealed a monoclonal T-cell clone, both supporting the diagnosis of an enteropathy associated T-cell lymphoma (EATCL). DIAGNOSIS AND THERAPY: The patient was enrolled in a study on intestinal non-Hodgkin lymphomas and accordingly received 6 courses of CHOP-chemotherapy. Clinical and histological improvement has lasted for over a year. CONCLUSION: Patients with coeliac disease unresponsive to a gluten-free diet or with a deteriorating clinical condition may have an enteropathy-associated T-cell lymphoma. This can manifest itself in the form of an ulcerative jejunitis. In the early stages of disease, immunhistochemical and molecularbiological analyses may lead to the correct diagnosis.

Celiac Disease↗