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Biomedical subjects

G Ott

Publications and source records attributed to G Ott.

At least 127 records · Page 7Linked to original sources
PubMed1994

The anaplastic variant of centrocytic lymphoma is marked by frequent rearrangements of the bcl-1 gene and high proliferation indices.

Ten cases of classic centrocytic lymphoma as defined in the Kiel classification system were investigated for their immunophenotype, their proliferation activity and by means of molecular diagnostics. The findings were compared to those obtained from a group of nine cases of anaplastic centrocytic lymphoma. Both groups showed virtually identical immunohistochemical characteristics with positivity for CD5 and negativity for CD10 and CD23. In the group of anaplastic centrocytic lymphoma, there were considerably higher proliferation indices as documented by staining for the Ki-67 antigen, up to 80% of the tumour cells being positive. Moreover, the cases of anaplastic centrocytic lymphoma had bcl-1 gene rearrangements in eight out of nine cases compared with three out of 10 cases of classic centrocytic lymphoma. DNA analysis was not able to detect bcl-2 gene rearrangement in any case, pointing to a difference compared with lymphomas of germinal centre origin. The coincidence of anaplastic and sometimes blast-like morphology of the tumour cells, high proliferation index and a rearranged bcl-1 gene in nearly all cases of anaplastic centrocytic lymphoma support their classification as high-grade malignant variants of centrocytic lymphoma and suggest a possible role for the bcl-1 locus not only in the origin but also in the progression of centrocytic lymphomas.

Aged↗
PubMed1994

Monoclonal Epstein-Barr virus genomes but lack of EBV-related protein expression in different types of gastric carcinoma.

Thirty-nine resection specimens of gastric carcinomas have been investigated for the presence of EBV RNA sequences using a highly sensitive non-radioactive in situ hybridization technique. Transcribed EBER sequences were found in seven (18%), including four cases of undifferentiated carcinoma with prominent lymphoid infiltration and three gastric adenocarcinomas. In the positive tumours all, or nearly all, tumour nuclei were distinctly labelled. No positive signals could be detected in the non-dysplastic epithelial cells or the reactive inflammatory infiltrate. Clonality analysis using specific probes to the variable tandem repeat region of the EBV yielded single episomal bands in all four cases tested, two of which were undifferentiated carcinomas and two adenocarcinomas. By means of immunohistology, no expression of the EBV-related proteins LMP or EBNA-2 was present in tumour cells of positive cases in in situ or blotting attempts. Our results suggest that infection of gastric carcinomas by the EB virus occurs early in tumourigenesis but, in contrast to nasopharyngeal carcinomas, does not result in the expression of EBV-specific proteins.

Adenocarcinoma↗
PubMed1994

[Chromosomal in situ hybridization and interphase cytogenetics in single cell and tissue section preparations: new methods in tumor diagnosis and clinical cytogenetics].

To overcome the shortcomings encountered in classical cytogenetics, a variety of in situ hybridization techniques have been developed enabling metaphase and interphase cytogenetics on routinely processed tissues and cells. These techniques comprise the detection of numerical chromosome aberrations, the delineation or "painting" of whole chromosomes or certain chromosome regions and the visualization of structural chromosome rearrangements in interphase nuclei. Some of these new methods can reliably be applied also on paraffin-embedded tissues, among them the comparative genomic in situ hybridization (CGH) technique suitable for providing a survey of over- or underrepresented genetic material on the chromosomal level even if only tumour DNA is available.

Chromosome Aberrations↗
PubMed1994

[Characterization of clonal B-cell populations in gastric MALT lymphomas and chronic gastritis by means of the polymerase chain reaction].

Amplification of the CDR3-region of the immunoglobulin (Ig) heavy chain gene rearrangement by means of the PCR yielded clonal products in the tumor DNA of 12 high or low grade gastric B-cell lymphomas of MALT-type. In four cases, additional clonal bands were found in different areas of tumor free mucosa diagnosed as chronic gastritis associated with Helicobacter pylori (HP). Most of these small clonal populations were found to share identical DNA sequences in their clone specific CDR3-regions with the main lymphoma in each patient; a finding consistent with the multifocal character of the disease. In two cases however, single clonal populations with different CDR3-regions revealed the existence of rare additional clonal B-cell-populations not related to the lymphoma and therefore possibly representing further independent foci.

B-Lymphocytes↗
PubMed1994

[Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

Autopsy↗
PubMed1994

Purine efflux from transplanted human cardiac allografts. Correlation with graft function.

Purine efflux from transplanted human cardiac allografts was investigated as a potential biochemical correlate to graft preservation and eventual function. Coronary sinus effluent from 14 allografts was sampled at 1, 5, 10, 15, 20, and 25 minutes after reperfusion. The plasma fraction from each sample was analyzed for hypoxanthine, xanthine, urate, inosine, and adenosine by high-performance liquid chromatography. Total organ preservation time, aortic crossclamp and bypass times, and initial cardiac index off bypass were recorded. An inotropic score was calculated from the dosages of inotropic agents each recipient required immediately after transplantation. Inosine and adenosine were not detectable in the coronary sinus effluent at any time during reperfusion. Hypoxanthine concentration rose sevenfold (p < 0.001) 1 minute after reperfusion. Xanthine concentration peaked later at 5 minutes after reperfusion, a twofold increase (p < 0.02). As reperfusion continued, hypoxanthine and xanthine concentrations returned toward baseline levels. The rise in coronary sinus xanthine concentration provides evidence for hypoxanthine degradation by xanthine oxidase during the immediate reperfusion period. The extent of hypoxanthine efflux correlated with total graft ischemic time (p < 0.05), inotropic score (p < 0.005), and the time from crossclamp release to cessation of bypass (p < 0.01). Hypoxanthine efflux can be used as a sensitive and objective biochemical indicator of graft preservation and immediate function.

Heart Transplantation↗
PubMed1993

Proton NMR studies of manganese ion binding to tRNA-derived acceptor arm duplexes.

Several RNA duplexes corresponding to the acceptor arms of different tRNAs have been analyzed with respect to their divalent metal ion binding capability by means of proton NMR spectroscopy using paramagnetic Mn2+ ions as probes. In particular, the role of GU wobble base pairs has been analyzed with reference to their potential for creating metal ion binding sites. It is shown that both the structural modifications induced by GU pairs in the A-RNA geometry and the sequence context seem to affect the metal ion binding capabilities.

Base Sequence↗
PubMed1993

Stability of triple helices containing RNA and DNA strands: experimental and molecular modeling studies.

UV-absorption spectrophotometry and molecular modeling have been used to study the influence of the chemical nature of sugars (ribose or deoxyribose) on triple helix stability. For the Pyrimidine.purine* Pyrimidine motif, all eight combinations were tested with each of the three strands composed of either DNA or RNA. The chemical nature of sugars has a dramatic influence on triple helix stability. For each double helix composition, a more stable triple helix was formed when the third strand was RNA rather than DNA. No stable triple helix was detected when the polypurine sequence was made of RNA with a third strand made of DNA. Energy minimization studies using the JUMNA program suggested that interactions between the 2'-hydroxyl group of the third strand and the phosphates of the polypurine strand play an important role in determining the relative stabilities of triple-helical structures in which the polypyrimidine third strand is oriented parallel to the polypurine sequence. These interactions are not allowed when the third strand adopts an antiparallel orientation with respect to the target polypurine sequence, as observed when the third strand contains G and A or G and T/U. We show by footprinting and gel retardation experiments that an oligoribonucleotide containing G and A or G and U fails to bind double helical DNA, while the corresponding DNA oligomers form stable triple-helical complexes.

Base Sequence↗
PubMed1993

The 3'-terminal end (NCCA) of tRNA determines the structure and stability of the aminoacyl acceptor stem.

We have done a systematic study on the contribution of the single-stranded NCCA end (where N is any nucleotide) to the stability of the aminoacyl stem of tRNA. A 7-bp RNA duplex with the single-strand ACCA 3' terminus derived from the aminoacyl stem of Escherichia coli tRNA(Ala) and several chemically synthesized sequence variants are characterized by proton NMR and thermodynamic parameters. The single-stranded 3' terminus noticeably stabilizes the duplex in a sequence-dependent manner. Though the largest contribution to the stability gain due to the ACCA end is provided by the first dangling 3' nucleotide, the influence of even the fourth nucleotide is measurable. The nature of the N73 discriminator base influences the stem structure and stability, which may be important for the recognition of tRNA by aminoacyl-tRNA synthetase. The stepwise attachment of the nucleotides to the 3' tail improves the stacking of the unpaired bases over the helix stem. Hence, the ACCA end appears to be structured. Replacing Mg2+ with Mn2+ causes broadening of certain imino proton peaks in the NMR spectrum, indicating a specific divalent metal ion binding site in the vicinity of the major identity element of the duplex (G3-U70) that is required for its recognition by the Ala-tRNA synthetase.

Amino Acyl-tRNA Synthetases↗
PubMed1993

Non-random integration of Epstein-Barr virus in lymphoblastoid cell lines.

In order to examine the role of Epstein-Barr virus (EBV) in the immortalization of human B lymphocytes and in the pathogenesis of lymphoid malignancies, we investigated whether the EBV integration into the human genome is randomly distributed or whether the virus integrates preferentially at certain sites. Twelve in vitro immortalized human lymphoblastoid cell lines (LCLs), two in vivo infected LCLs, and one Burkitt's lymphoma cell line (EB2) were examined by non-radioactive in situ hybridization (ISH) with a biotinylated EBV probe. Recurrent hybridization sites were detected in all 15 cell lines. The chromosomes frequently carrying the EBV genome were chromosomes 1, 2, 4, and 5. In more than 70 chromosomal bands, a greater number of integration sites than expected was found (p < 0.05). Approximately half of these bands were involved in the majority of the cell lines (for example, 1p31, 1q43, 2p22, 3q28, 4q13, 5p14, 5q12, and 11p15) whereby band 5p14 was involved in all LCLs analyzed. Virtually no viral integrations were found on the sex chromosomes (X, Y). The majority of the EBV integrations was found in G-band-positive material (p < 0.0001). Thus, our findings clearly show that EBV integrates into the human genome in a non-random manner.

Adolescent↗
PubMed1993

Primary gastric lymphoma is rarely associated with Epstein-Barr virus.

Recently, the association of Epstein-Barr virus (EBV) with undifferentiated lymphoepithelioma-like carcinoma and adenocarcinoma of the stomach has been described. In this study of 55 primary gastric lymphomas, most of them belonging to the group of MALT lymphomas, the question of possible EBV involvement has been addressed using in-situ hybridization (ISH) and blot techniques. EBV DNA and/or DNA sequences were found in only two of 24 centroblastic and B-immunoblastic lymphomas and in one anaplastic large cell lymphoma of null cell phenotype. In a further centroblastic lymphoma, a few positive nontumorous (bystander) cells were identified by ISH. By means of ISH, no positive signals could be detected in the preserved overlying mucosa nor in regenerating epithelium adjacent to lymphoma-induced ulcerations.

Blotting, Southern↗
PubMed1993

EBV DNA in nodal and extranodal non-Hodgkin's lymphomas: impact of cell lineage, morphology, and site of origin.

The Epstein-Barr virus (EBV) is a transforming herpes virus which is found in high frequencies in lymphoproliferative disorders arising in immunocompromised patients. To address the question of viral involvement in lymphomas of immunocompetent patients, we investigated 299 nodal and extranodal non-Hodgkin's, non-Burkitt's lymphomas of B- and T-cell lineage for the presence of EBV DNA. Epstein-Barr nucleic acid sequences were detected in 23 of 226 (10%) cases of B-cell lymphomas, in 24/72 (33%) T-cell lymphomas and one non-B, non-T lymphoma. Our data imply a possible role for the EBV in lymphoma development or propagation, an influence of viral factors on morphology and an impact of the anatomic site in which lymphoma development occurs.

Cell Transformation, Neoplastic↗
PubMed1993

Tc-99m labeled monoclonal antibodies against granulocytes (BW 250/183) in the detection of appendicitis.

Scintigraphy with Tc-99m labeled antigranulocyte antibodies (BW 250/183 MoABs) was performed in 32 patients with suspected appendicitis. Abdominal imaging (planar/SPECT) was performed 2 hours after injection of the tracer. All patients also had surgery and a histologic examination of the resected tissue. Of the patients, 17 suffered from "acute appendicitis" and 12 had right positive scans (sensitivity = 70.6%). In 15 patients, acute appendicitis could have been ruled out, and in 11 of these cases the scan was true negative (specificity = 73.3%). The overall accuracy was 71.8% (23/32 cases). The use of Tc-99m antigranulocyte MoABs may overcome the problems associated with the Tc-99m HMPAO granulocyte and In-111 oxine approaches, which include nonspecific intestinal activity or the lack of timeliness. The use of Tc-99m labeled antigranulocyte antibodies is suitable as an emergency procedure and may play a role in the management of patients with suspected appendicitis.

Adolescent↗
PubMed1993

Human herpesvirus-6 and Epstein-Barr virus genome in primary cerebral lymphomas.

Using dot blotting, we found Epstein-Barr virus genome in three AIDS-related primary cerebral lymphomas (PCLs), but in none of 39 sporadic PCLs. Human herpesvirus-6 sequences were present only in one sporadic PCL, as revealed by polymerase chain reaction and Southern analysis. We conclude that these viruses do not appear to play a major role in PCL pathogenesis in immunocompetent subjects.

Aged↗
PubMed1992

Prevalence of Epstein-Barr virus DNA in different T-cell lymphoma entities in a European population.

The Epstein-Barr virus (EBV) has been classically associated with nasopharyngeal carcinoma and Burkitt's lymphoma, a monoclonal B-cell non-Hodgkin's lymphoma. Since the EBV genome has also been found in post-transplant lymphomas and lymphomas arising in individuals infected with the human immunodeficiency virus, evidence has now accumulated that EBV might be the initiator of a multi-step process leading from polyclonal B-cell hyperplasias to monoclonal lymphoma. In a retrospective study of 60 T-cell lymphomas of various types, we found EBV DNA in 21 (35%) using Southern- and/or dot-blot techniques. Eight of 14 nodal samples of angio-immunoblastic lymphadenopathy (57%) were shown to harbour detectable EBV DNA. The tumour with the next highest frequency, 47% (7/15 cases analyzed) was pleomorphic T-cell lymphoma, medium- and large-cell type; EBV was found both in nodal and in extranodal lymphomas of this type. Lymphoepitheloid (Lennert's) lymphoma and large-cell anaplastic lymphoma were positive in 2/5 and 3/8, respectively, of the cases analyzed. No viral DNA could be demonstrated in 3 T-immunoblastic and 5 T-lymphoblastic lymphomas. Clonotypic analysis revealed monoclonal as well as oligoclonal virus populations. Our data suggest that, at least in some of these entities, the presence of the EBV genome might be due to secondary mechanisms such as escape from immune surveillance.

DNA, Viral↗
PubMed1992

Glossodynia--psychodynamic basis and results of psychopathometric investigations.

Between 1985 and 1988, 131 patients suffering from glossodynia were submitted to a careful examination that included a neurological work-up, a detailed psychiatric interview and a number of psychological tests. Particular attention was paid to psychosomatic and psychopathologic disorders. The average age of the patients was 55 yr, and 73% of them were female. In 40% of patients, the psychiatric interview revealed no psychopathological findings, while in most of them, a psychiatrically relevant disorder, usually depression, was found. All patients had an unremarkable neurological status, and the EEG's showed no pathological changes. Psychodynamic considerations in conjunction with the elevated scores for depressive mood, anxiety and tension suggest that glossodynia is an expression of a psychosomatic disorder.

Adult↗