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  • 1
    Online Resource
    Online Resource
    Berlin, Heidelberg :Springer Berlin / Heidelberg,
    Keywords: Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (106 pages)
    Edition: 1st ed.
    ISBN: 9783642700972
    Language: German
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  • 2
    ISSN: 1437-160X
    Keywords: bcl-2 ; Lymphocyte subsets ; Synovial inflammation ; Rheumatoid arthritis ; Germinal center
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We used a double-immunostaining technique to analyze the distribution of bcl-2+ B and T lymphocytes within the synovial membranes (SM) of 13 patients with rheumatic diseases: 11 with rheumatoid arthritis (RA), 1 with ankylosing spondylitis (AS), and 1 with osteoarthritis (OA). A high proportion (up to 50%) of the lymphocytes belonged to the B cell subset. Most of both T and B lymphocytes were positive for the bcl-2 protein. In germinal centers B lymphocytes were also negative for bcl-2 protein expression, comparable to the situation in germinal centers of secondary lymphatic organs. We conclude that bcl-2+ B lymphocytes are submitted to antigen selection in the inflamed SMs while bcl-2+ protein expression provides survival signals for their persistence in the infiltrates. The expression of bel-2 may be an important factor in protecting lymphocytes in SM from apoptosis by glucocorticoids, cytostatic drugs, and irradiation.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Keywords: clonal heterogeneity ; Hodgkin's disease ; NPM/ALK ; single cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The translocation t(2;5)(p23;q35) leads to the fusion of thenucleophosmin gene (NPM) on chromosome 5q35 to the recently describedreceptor kinase ALK 2p23. It is characteristic of a subgroup of CD30+large-cell anaplastic non-Hodgkin's lymphoma (ALCL). Since some cases ofHodgkin's disease (HD) and ALCL share common features, a common pathogenesishas been proposed in a report of the expression of NPM/ALK fusion mRNA in11/13 Hodgkin's lymphomas. Patients and methods: We approached this question by micromanipulatoryisolation of single Hodgkin and Reed–Sternberg (H-RS) cells andsubsequent RT-PCR amplification of NPM/ALK fusion cDNA from these singlecells. Results: Specificity of cell selection was shown by the HD-specificpattern of EBV-gene expression in single H-RS cells. In 4 out of 7 cases,NPM/ALK fusion cDNA was detected in the RNA from whole lymph node tissue. In2 out of 9 cases, NPM/ALK fusion sequences were amplified from single H-RScells, albeit in a very low frequency (〈5%). Conclusions: These data indicate that NPM/ALK fusion transcripts donot play an early role in the pathogenesis of HD. Whether the rare expressionof NPM/ALK is the result of clonal heterogeneity or an indication for clonalevolution and progression toward ALCL can only be answered by the repeatedanalysis of indicator cases during the course of the disease.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1437-160X
    Keywords: Key words VH gene repertoire ; Immunoglobulin gene rearrangements ; Rheumatoid arthritis ; Somatic mutation ; Memory B cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The VH gene (Variable gene segments of the heavy chain locus) repertoire can be investigated by DNA analysis of rearranged immunoglobulin VH genes, which also allows for an indirect estimation of antibody selection by analysis of somatic mutations. Using a polymerase chain reaction (PCR) it is also possible to analyse these genes in small numbers of cells or even single cells. This approach was chosen to investigate germinal centre like lymphocyte follicles in the synovial membranes of two patients with rheumatoid arthritis (RA) in order to analyse the local humoral immune response in RA. Individual B-cell aggregates of synovial membrane of two patients with RA were isolated by micromanipulation from microscopic slides. VH-DH-JH (variable, diversity, and joining segments of the heavy chain locus) rearrangements in all possible VH-JH combinations were amplified from these B cell foci, cloned and subjected to sequence analysis. Sequence analysis revealed that most of the rearranged VH genes were somatically mutated with at least 1% (range 1.3 – 14.9%) somatic mutations and therefore were derived from antigen-selected memory B cells. Intraclonal diversity in one-third of the clones indicated the generation of memory B cells in the synovial membrane and characterized the synovial membrane as lymphatic tissue where secondary immune responses to an as yet unknown antigen take place.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Rheumatology international 17 (1997), S. 127-130 
    ISSN: 1437-160X
    Keywords: Key words Aspergillosis ; Opportunistic infections ; Pancytopenia ; Systemic lupus erythematosus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report on the case of a 25-year-old female with severe systemic lupus erythematosus (SLE) who presented with pancytopenia, fever, arthralgia and abdominal pain. After antibiotic treatment, the patient was afebrile for 3 days before her temperature rose again. Dyspnoea and cough pointed towards pneumonia which was confirmed by X-ray. Different antibiotics and the antimycotic agent fluconazol were given. The lupus flare was treated with high-dose prednisolone. After a couple of days, the dyspnoea increased and mechanical ventilation became necessary. Bronchoscopy and transbronchial biopsy revealed the diagnosis of invasive aspergilloses. Despite of an immediate treatment with amphotericin B, the patient died because of respiratory insufficiency. The literature on aspergillosis in SLE is reviewed and prophylactic, diagnostic and therapeutic options are discussed for this infectious complication which has an 80% mortality in patients with SLE.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1569-8041
    Keywords: chronic lymphocytic leukaemia ; epirubicin ; fludarabine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Fludarabine has been reported to be the most effective single-agent in previously treated chronic lymphocytic leukaemia (CLL). Based on the in vitro synergism of fludarabine with anthracyclines and on results showing a higher efficacy of CHOP against COP we attempted to improve treatment results with a combination of fludarabine and an anthracycline. Patients and methods: The aim of the multicenter study was to evaluate the rate and duration of remissions and investigate the toxic and immunosuppressive effects of fludarabine and epirubicin in the treatment of CLL in Binet stages B and C as first-line therapy or in first relapse. Thirty-eight patients were treated with fludarabine 25 mg/m2 on days 1–5 and epirubicin 25 mg/m2 on days 4 and 5. Results: The overall response rate (OR) was 82% (95% confidence interval (95% CI): 66%–92%) with a CR rate of 32% (95% CI: 18%–49%). For the 25 previously untreated patients the OR was 92% (95% CI: 74%–99%) including 40% CRs (95% CI: 21%–61%). Granulocytopenia grade 3 occurred in 23% of all evaluable cycles, and grade 4 in 17%. The median remission duration was 19 months (range 6–37 months). Conclusion: The results show that the combination of fludarabine and epirubicin is tolerable and highly effective in the treatment of CLL. With the addition of epirubicin to fludarabine, it appears possible to achieve a higher response rate and a more rapid response, especially of nodal manifestations. This regimen can be administered in an outpatient facility except for the first cycle because of the risk of a tumour lysis. The possible benefit of the combination presented here in the treatment of CLL in comparison to single-agent fludarabine treatment is presently under study in a prospective randomised multicenter study.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: At present, treatment results for patients withadvanced-stage Hodgkin's disease remain unsatisfactory. Standard chemotherapyM(C)OPP (nitrogen mustard (cyclophosphamide), vincristine, procabazine, andprednisone), ABVD (adriamycine, bleomycine, vinblastine, and dacarbacine) orM(C)OPP/ABVD +/− radiotherapy fail to achieve long-term completeremission in 35% to 50% of these patients. The BEACOPP(bleomycin, etoposide, adriamycine, cyclophosphamide, vincristine,procarbazine, and prednisone) regimen was developed to improve treatmentresults by dose intensification achieved by reduced duration of treatment(time intensification) and addition of etoposide. Patients and methods: Thirty untreated patients with advancedHodgkin's disease stage IIB–IV according to the Ann Arbor classificationwere treated with the time intensified BEACOPP regimen. Each patient wasscheduled to receive eight cycles of chemotherapy with consolidatingradiotherapy to sites of initial bulk disease and to residual tumor remainingafter chemotherapy. Results: All patients were evaluable for assessment of toxicity,treatment response, freedom from treatment failure (FFTF) and survival (SV).Of 30 treated patients, 29 patients received the intended eight cycles ofBEACOPP. One patient, in clinical CR, terminated the chemotherapy at his ownrequest after six cycles and is at this time, 48 months after the end oftreatment, in complete remission. Toxicity was tolerable with WHO grade 3/4leucopenia in 28% of chemotherapy cycles and one severe (WHO grade 3)infection. No treatment-related death occurred. Cycles could generally begiven on schedule. Complete remission (CR) was achieved in all but twopatients (93%). At present, only one patient has relapsed. At a medianfollow-up of 40 months, FFTF-rate is 89% (lower confidence limit:80%). One patient died due to progressive disease. Conclusion: The BEACOPP regimen is feasible at moderate hematopoeitictoxicity. With a FFTF-rate of 89% at a median follow-up of 40 months,the treatment results are very encouraging. A prospective randomised trial hasbeen initiated to compare the BEACOPP regimen with the standard COPP/ABVDregimen in advanced-stage Hodgkin's disease.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1569-8041
    Keywords: clonal heterogeneity ; Hodgkin's disease ; NPM/ALK ; single cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The translocation t(2;5)(p23;q35) leads to the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to the recently described receptor kinase ALK 2p23. It is characteristic of a subgroup of CD30+large-cell anaplastic non-Hodgkin's lymphoma (ALCL). Since some cases of Hodgkin's disease (HD) and ALCL share common features, a common pathogenesis has been proposed in a report of the expression of NPM/ALK fusion mRNA in11/13 Hodgkin's lymphomas. Patients and methods: We approached this question by micro manipulatory isolation of single Hodgkin and Reed–Sternberg (H-RS) cells and subsequent RT-PCR amplification of NPM/ALK fusion cDNA from these single cells. Results: Specificity of cell selection was shown by the HD-specific pattern of EBV-gene expression in single H-RS cells. In 4 out of 7 cases, NPM/ALK fusion cDNA was detected in the RNA from whole lymph node tissue. In2 out of 9 cases, NPM/ALK fusion sequences were amplified from single H-RS cells, albeit in a very low frequency (〈5%). Conclusions: These data indicate that NPM/ALK fusion transcripts do not play an early role in the pathogenesis of HD. Whether the rare expression of NPM/ALK is the result of clonal heterogeneity or an indication for clonal evolution and progression toward ALCL can only be answered by the repeated analysis of indicator cases during the course of the disease.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 39 (1979), S. 141-145 
    ISSN: 1432-0584
    Keywords: Alkalische Leukozytenphosphatase (ALP) ; maligne Erkrankungen ; Metastasen ; Leukocyte alkaline phosphatase (LAP) ; Malignant disease ; Metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The leukocyte alkaline phosphatase (LAP) levels were determined in 183 patients with malignant diseases and 71 normal controls. The median LAP scores were 64 units (range 0 to 290) for the patients and 55 (range 2 to 158) for the controls, respectively, and no significant difference could be established. When analyzed according to primary malignancy, only in patients with Hodgkin's disease (n = 14) was the median value higher than normal (p 〈 0.001). In patients with distant metastases (n = 48), higher LAP levels were demonstrated (M = 76, range 21 to 290) as compared to patients with no evidence of metastases (M = 53, range 0 to 229), (p 〈0.01). Thus, LAP activity has very limited value in the diagnosis of malignancies. Its elevation in the presence of malignant disease might, however, indicate metastases.
    Notes: Zusammenfassung Bei 183 Patienten mit malignen Erkrankungen und 71 Kontrollpersonen wurde der ALP-Index untersucht. Der Median für die Patienten war 64 (range 0–290) und für die Kontrolle 55 (range 2–158). Dieser Unterschied ist jedoch statistisch nicht signifikant. Bei der Analyse der ALP-Indices nach Tumorgruppen konnte eine signifikante Erhöhung des ALP-Index nur bei Morbus Hodgkin (n = 14) festgestellt werden (p 〈0,001). Der ALP-Index war auch bei Patienten mit Metastasen (n = 48) (M = 76, range 21 zu 290) im Vergleich zum ALP-Index bei Patienten ohne Metastasen (n = 118, M = 53 range 0–229) erhöht (p 〈0,01). Die ALP-Aktivität hat also nur einen beschränkten Wert in der Diagnostik bei malignen Erkrankungen. Eine Erhöhung kann jedoch auf das Vorliegen von Metastasen hinweisen.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Cancer Genetics and Cytogenetics 69 (1993), S. 126-128 
    ISSN: 0165-4608
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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