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991.
C. Müller P. Ostendorf P. Wernet K. Schüch H. Wahl H. D. Waller 《Journal of molecular medicine (Berlin, Germany)》1984,62(14):675-688
Summary Skin biopsies of 26 patients with leukemia and seven patients with aplastic anemia were investigated before and at different stages after allogeneic bone marrow transplantation (BMT) to establish the immunological criteria which distinguish skin alterations during normal reconstitution from dermal lesions mediated by graft-versushost disease (GvHD). Of the 33 patients studied 27 presented with clinically diagnosed acute and/or chronic GvHD, one patient died of bone marrow rejection. Immunohistological analysis of the respective skin biopsies with selected monoclonal antibodies against human leukocyte antigens (HLA) and differentiation antigens of the lympho-hematopoietic cells revealed low dermal mononuclear cell counts with phenotypically normal constituents in five cases with uncomplicated reconstitution post-grafting. In contrast, increased dermal cellular infiltrates predominantly consisting of Lyt 3+, OKT 8+ T-lymphocytes, as well as of a large number of Ia-like (immune response associated = HLA-D) determinant+ monocytes/macrophages were observed in all patients with active acute/chronic GvH reactivity. As sign of activation simultaneous expression of HLA-D region products was also found on a subset of the invading OKT 8+ T-lymphocytes. Progression of GvHD was associated with additional surface staining of keratinocytes for Ia-like determinants. Loss of Ia-like determinant+, OKT 6+ dentritic epithelial cells in all leukemic patients, as well as in patients with aplastic anemia with or without GvHD suggested damage of Langerhans cells due to the previous radiotherapy and/or specific immunological destruction. In patients with fatal outcome of GvHD prolonged reduction of these dentritic epithelial cells seemed to be indicative of impaired immune reconstitution or bone marrow dysfunction. Thus immunopathological features of skin GvHR may enable early recognition and prognostic evaluation of this disease possibly allowing more effective therapy.Abbreviations GvHD
graft-versus-host disease
- GvHR
graft-versus-host reactivity
- SAA
severe aplastic anemia
- TBI
total body irradiation
- BMT
bone marrow transplantation
- HLA
human leukocyte antigens
- Ia-like antigens
Immune-response-associated antigens
- PBS
phosphate buffered saline
- FITC
fluorescein isothiocyanate
- TRITC
tetramethylrhodamine isothiocyanate
Supported by DFG Sonderforschungsbereich 120, Projekt A 2 and B 1Dedicated to Prof. Dr. Dr. h.c. H.E. Bock on the occasion of his 80th birthday 相似文献
992.
993.
E. Kleihauer H. D. Waller H. Chr Benöhr E. Kohne P. Gelinsky 《Journal of molecular medicine (Berlin, Germany)》1971,49(11):651-658
Zusammenfassung Bericht über eine neue-Kettenvariante in einer in Süddeutschland ansässigen Familie. Von insgesamt sieben eingehend untersuchten Familienmitgliedern konnte die Anomalie in der heterozygoten Form bei zwei Angehörigen (Mutter und Sohn) nachgewiesen werden. Der Erbgang ist autosomal dominant. Das anomale Hämoglobin verursacht bei den Teilträgern infolge erhöhter Spontanoxydation eine Methämoglobinämie mit sichtbarer Cyanose sowie eine leichte kompensierte hämolytische Anämie ohne Innenkörperbildung. Der anomale Blutfarbstoff ist hitzelabil. Ein Enzymdefekt der Erythrocyten einschließlich Diaphorasemangel konnte ausgeschlossen werden. Globinanalysen ergaben einem im core ( Tp 10–12, Aminosäurenposition 83 bis 120) der-Kette gelegenen Defekt. Die Anomalie, die mit keiner der bisher bekannten Strukturvarianten übereinstimmt, wurde nach dem Ort des Auffindens als Hb Tübingen bezeichnet.
Herrn Prof. Dr. K. H. Schäfer, Hamburg, zum 60. Geburtstag.
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
Hb Tübingen. A new-chain variant ( Tp 10–12) showing increased spontaneous oxidation
Summary Hemoglobin Tübingen, a new-chain variant ( Tp 10–12) was discovered in two members out of seven of a German family. The abnormal hemoglobin is characterized by increased spontaneous oxidation, heat instability, normal methemoglobin spectrum, and the absence of spontaneous Heinz body formation. The carriers suffer from a mild and compensated hemolytic anemia; the main clinical symptom is a mild cyanosis. The amount of abnormal hemoglobin was approximately 40 per cent when DEAE-chromatography was performed with methemoglobin hemolysates; no separation could be achieved using hemolysates in the cyanmethemoglobin form. It was not possible to separate the abnormal-chain from normal-chain by globin electrophoresis or by chromatography on CM 52. Globin analyses showed a defect located in the core of the-chain ( Tp 10–12, amino acid position 83–120). This anomaly which does not correspond to any of the structural variants known so far was named Hb Tübingen according to the city in which it was found.
Herrn Prof. Dr. K. H. Schäfer, Hamburg, zum 60. Geburtstag.
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
994.
Edmund K. Waller David Miklos Corey Cutler Mukta Arora Madan H. Jagasia Iskra Pusic Mary E.D. Flowers Aaron C. Logan Ryotaro Nakamura Stephen Chang Fong Clow Indu D. Lal Lori Styles Samantha Jaglowski 《Biology of blood and marrow transplantation》2019,25(10):2002-2007
Chronic graft-versus-host disease (cGVHD) is a life-threatening complication of allogeneic stem cell transplantation. In a Phase 1b/2, open-label study (PCYC-1129; ClinicalTrials.gov identifier NCT02195869) involving 42 patients with active cGVHD who were steroid-dependent or -refractory, the activity and safety of ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, was demonstrated. Here we report extended follow-up for patients in this study. After a median follow-up of 26 months (range, .53 to 36.7 months), best overall response rate in the all treated population was 69% (29 of 42), with 13 patients (31%) achieving a complete response and 16 patients (38%) achieving a partial response. Sustained responses of ≥20, ≥32, and ≥44 weeks were seen in 20 (69%), 18 (62%), and 16 (55%) of the 29 responders, respectively. Of 26 patients with ≥2 involved organs, 19 (73%) showed responses in ≥2 organs. Six of 10 patients (60%) with ≥3 involved organs showed responses in ≥3 organs. Eleven of 18 patients (61%) who had sclerosis at baseline showed a sclerotic response (39% with complete response, 22% with partial response). Twenty-seven of 42 patients (64%) reached a corticosteroid dose of <.15 mg/kg/day during the study; 8 discontinued corticosteroid treatment and remained off corticosteroid at study closure. Safety findings for this updated analysis were consistent with the safety profile seen at the time of the original analysis. Common grade ≥3 adverse events (AEs) were pneumonia (n = 6), fatigue (n = 5), and diarrhea (n = 4). The onset of new grade ≥3 AEs decreased from 71% in the first year of treatment to 25% in the second year (n = 12). AEs leading to discontinuation occurred in 18 patients (43%). At a median follow-up of >2 years, ibrutinib continued to produce durable responses in patients with cGVHD who had failed previous systemic therapy. In this pretreated, high-risk population, clinically meaningful benefit and an acceptable safety profile were observed with additional follow-up for ibrutinib. These results demonstrate a substantial advance in the therapeutic management of patients with cGVHD. 相似文献
995.
G. W. Löhr H. D. Waller O. Karges 《Journal of molecular medicine (Berlin, Germany)》1957,35(17):871-875
Zusammenfassung 1. Es wurde in gewaschenen Erythrocyten von Gesunden der Gehalt an Aldolase, Trioseisomerase, Phosphoglyceraldehyddehydrogenase, Milchsäuredehydrogenase und Hämiglobinreduktasesystem bestimmt.2. Die gefundenen Fermentaktivitäten wurden auf die Zellzahl, den Hämoglobingehalt und das Erythrocyteneinzelvolumen berechnet.3. Unter Zugrundelegung der Umsatzzahlen für kristalline Fermente wurde der Anteil der einzelnen Gärungsfermentproteine am Gesamteiweiß und Nichthämoglobineiweiß der Erythrocyten bestimmt und mit den entsprechenden Daten des Muskels verglichen.4. Im Erythrocyten und Reticulocyten wurden weder löslichel--Glycerophosphatdehydrogenase (Baranowski-Enzym) noch strukturgebundenel--Glycerophosphatdehydrogenase (Green-Enzym) gefunden.l--Glycerophosphat war ebenfalls nicht nachweisbar.5. Die begrenzenden Reaktionsstufen der Glykolyse im Erythrocyten sind nach unseren Fermentuntersuchungen die Aldolase- und die oxydierende Gärungsfermentreaktion. 相似文献
996.
R. Gross W. Gerok G. W. Löhr W. Vogell H. D. Waller W. Theopold 《Journal of molecular medicine (Berlin, Germany)》1960,38(5):193-206
Ohne ZusammenfassungDie Untersuchungen wurden in Teilen durch Beihilfen der Deutschen Forschungsgemeinschaft und des Marburger Universitätsbundes unterstützt05-3-23 16:51. Der Deutschen Laevosan-Gesellschaft und der Fa. C. F. Boehringer Mannheim haben wir für die großzügige Überlassung von Fermenten, Cofermenten und Substraten zu danken. 相似文献
997.
H. D. Waller B. Schlegel A. A. Müller G. W. Löhr 《Journal of molecular medicine (Berlin, Germany)》1959,37(17):898-900
Zusammenfassung Der Hämiglobingehalt ist in alternden Erythrocyten höher als in jungen roten Blutzellen. Der Anteil des Hämiglobins am Gesamthämoglobin steigt in einer Erythrocytenpopulation bei intravitaler Alterung von 80 Tagen von 0,01 auf etwa 0,08 an. Der anstieg des Hämiglobins wird von den Verfassern durch den Aktivitätsverlust der DPNH2-liefernden Reaktionen im Erythrocyten, die den Wasserstoff für die Hämiglobinreduktion bilden, erklärt. 相似文献
998.
Effects of telomerase modulation in human hematopoietic progenitor cells 总被引:15,自引:0,他引:15
Zimmermann S Glaser S Ketteler R Waller CF Klingmüller U Martens UM 《Stem cells (Dayton, Ohio)》2004,22(5):741-749
Loss of telomeric repeats has been causally linked to replicative senescence and aging in human cells. In contrast to normal somatic cells, which are telomerase-negative, hematopoietic stem cells have low levels of telomerase, which can be transiently upregulated upon cytokine stimulation. To examine whether ectopic expression of telomerase can overcome telomere erosion in hematopoietic progenitor cells, we overexpressed telomerase in CD34+ and AC133+ cord blood (CB) cells using retroviral vectors containing hTERT, the catalytic component of telomerase. Although the hTERT-transduced CB cells exhibited significantly elevated telomerase activity (approximately 10-fold), the mean telomere length was only increased up to 600 bp, which was in contrast to hTERT-transduced fibroblast cells gaining more than 2-kb telomeric repeats. Moreover, ectopic telomerase activity did not prevent overall telomere shortening, which was in the range of 1.3 kb in serum-free expansion culture. We also blocked endogenous telomerase activity by ectopic expression of dominant-negative hTERT. Whereas CB cells with absent telomerase activity showed reduced absolute numbers of colony-forming cells, we observed increased rates only for burst-forming units erythroid when the enzyme was overexpressed. These results suggest that telomere shortening in human hematopoietic progenitor cells cannot be compensated by increased levels of telomerase alone and is likely to be dependent on other factors, such as telomere binding proteins. Furthermore, telomerase function seems to be directly associated with the proliferative capacity of stem cells and may exert an additional role in lineage differentiation. 相似文献
999.
1000.
Jennie Sines Professor Glenn Waller Caroline Meyer Laura Wigley 《Psychology and psychotherapy》2008,81(2):121-129
Objectives . Narcissism is a personality trait that can interfere with the application of evidence‐based therapies for the eating disorders, influencing collaboration and the patient's willingness to take responsibility for participating in change. In order to understand and work with this personality characteristic, it is important to understand the cognitions that underpin the traits concerned. Design . This study examined the associations between schema‐level core beliefs and narcissism in eating disorders. Narcissism was conceptualized in terms of both its core element (entitlement and grandiosity) and the narcissistic defences (‘bad you’ and ‘poor me’ attitudes). Methods . Validated measures of the different elements of narcissism and of core beliefs were completed by 80 eating‐disordered patients and 70 non‐clinical comparison women. Multiple regression analyses were used to determine the core beliefs associated with each aspect of narcissism. Results . The pattern of association differed across the two groups. Among the eating‐disordered women, different core beliefs were associated with core narcissism and with each of the two defences. Conclusions . Unconditional schema‐level beliefs are associated with narcissistic personality traits in the eating disorders suggesting that these therapy‐interfering personality characteristics might be addressed by modifying the relevant core beliefs, thus making it possible to work more directly with the eating disorder itself. 相似文献