Evaluation of biologic activity of tryptase secreted from blast cells in acute myeloid leukemia

A number of autocrine and paracrine growth regulators are considered to be involved in the survival and proliferation of blast cells in acute myeloid leukemia (AML). We have recently shown that blast cells in a group of patients with AML produce and secrete the mitogenic enzyme tryptase. In the present study, we examined functional effects of tryptase in the context of AML. As assessed by 3H-thymidine uptake experiments, tryptase-containing serum from patients with AML as well as heparin-complexed recombinant tryptase were found to promote the proliferation of cultured bone marrow- and lung fibroblasts in a dose-dependent manner. A neutralizing antibody against human beta-tryptase was found to diminish these growth-stimulatory effects of serum-tryptase in all patients examined. Tryptase also induced the expression of mRNA for GM-CSF and SCF, two cytokines known to promote growth of AML cells, in cultured bone marrow fibroblasts. Neither recombinant tryptase nor tryptase-rich serum of AML patients, showed an effect on the growth of leukemic blast cells irrespective of the FAB category or expression of protease-activated receptor (PAR)-2, a putative molecular target of tryptase. Together, tryptase is secreted from AML blasts as a biologically active molecule that may exhibit paracrine rather than autocrine effects in AML.     

Cortical porosity of the mandible in an osteoporotic sheep model

Objectives: Cortical porosity and thickness of the axial and the appendicular skeleton are predictors of osteoporotic fractures. In the jawbone, however, cortical porosity and thickness may affect the mechanical stability of dental implants. We have shown previously that the jawbone of osteoporotic sheep has impaired trabecular structures, but whether catabolic bone turnover also accounts for the cortical bone porosity remains unknown. Material and methods: We compared mandibular bone from six geriatric sheep subjected to ovariectomy, calcium/vitamin D restriction, and methylprednisolone administration to those of six healthy adult control sheep. Histological ground sections were prepared from the diastema, first and second premolars, and postmolar region. Cortical porosity and thickness were assessed by histomorphometry. Results: Cortical porosity was higher in osteoporotic sheep than in adult controls in the diastema and in the first and second premolar region. In the postmolar region, the difference failed to reach the level of significance. The changes were even more prominent when histomorphometry was restricted to the inner millimeter of the mandibular cortex. In contrast, induction of osteoporosis did not have a discernable effect on cortical thickness. Conclusion: These results demonstrate that cortical porosity of mandibles is more pronounced in geriatric osteoporotic sheep than in adult controls. To cite this article:
Dvorak G, Reich KM, Tangl S, Goldhahn J, Haas R, Gruber R. Cortical porosity of the mandible in an osteoporotic sheep model.
Clin. Oral Impl. Res 22 , 2011; 500–505
doi: 10.1111/j.1600‐0501.2010.02031.x     

Antimycobacterial immune responses in patients with pulmonary sarcoidosis

Introduction: Sarcoidosis is a multisystem granulomatous disease of unknown origin. Pathogenetic involvement of Mycobacterium tuberculosis has frequently been discussed in the aetiology of sarcoidosis; however, studies still remain contradictory. Objective: We addressed the question of mycobacterial involvement in the pathogenesis of sarcoidosis by analysing cellular immune responses to mycobacterial antigens. Methods: We examined the interferon (IFN)‐γ production by enzyme‐linked immunospot in response to purified protein derivate (PPD) mycobacterial‐specific antigen early secretory antigenic target (ESAT)‐6 and culture filtrate protein (CFP)‐10 by peripheral blood mononuclear cells (PBMCs) and bronchoalveolar‐lavage mononuclear cells (BALMCs) of patients with pulmonary sarcoidosis, smear‐negative tuberculosis and controls. Results: Release of IFN‐γ in response to ex vivo contact with PPD, ESAT‐6 or CFP‐10 by BALMC and PBMC were comparable among patients with sarcoidosis and controls (PBMC P = 0.2326; BALMC P = 0.1767) and were less frequently observed in both groups compared to patients with tuberculosis (BALMC P < 0.05; PBMC P < 0.0001). Within PBMC, the immunophenotype of sarcoidosis patients differed from that of patients with tuberculosis, as well as from that of controls, while within BALMC it resembled that of patients with tuberculosis. Conclusion: In contrast to patients with tuberculosis, the frequency of mycobacteria‐specific local and systemic immune responses is not elevated in patients with sarcoidosis when compared to controls. The immunophenotype represents the local resemblance of the granulomatous reaction underlying tuberculosis and sarcoidosis while showing systemical difference. These observations do not support a role of an infection with M. tuberculosis in the pathogenesis of sarcoidosis. Please cite this paper as: Hörster R, Kirsten D, Gaede KI, Jafari C, Strassburg A, Greinert U, Kalsdorf B, Ernst M and Lange C. Antimycobacterial immune responses in patients with pulmonary sarcoidosis. The Clinical Respiratory Journal 2009; 3: 229–238.     

Successful treatment of hereditary angioedema with bradykinin B2‐receptor antagonist icatibant

The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.