Biological functions of serine proteases in mast cells in allergic inflammation

Serine proteases in mast cell granules, such as chymase, atypical chymase, and tryptase, which are major proteins in the granules, may play important roles in the process of immunoglobulin E (IgE)-mediated degranulation and in pathobiological alterations in tissues. Indeed, inhibitors of chymase, substrate analogs, and antichymase F(ab')2, but not inhibitors of tryptase, markedly inhibited histamine release induced by IgE-receptor bridging but not that induced by Ca ionophore. In contrast, inhibitors of metalloprotease inhibited histamine release induced not only by IgE-receptor bridging but also by Ca ionophore. These results suggest that chymase and metalloprotease are involved at different steps in the process of degranulation. The extents of inhibition of histamine release were closely correlated with the amounts of the inhibitors of chymase accumulated in the granules. After degranulation, the released proteases may in part contribute to pathobiological alterations in allergic disorders through generations of C3a anaphylatoxin and thrombin by human and rat tryptase, respectively, and those of angiotensin II and a chemotactic factor of neutrophils by human and rat chymase, respectively. Moreover, chymase and atypical chymase from rat were shown to destroy type IV collagen, and human tryptase was found to hydrolyze various plasma proteins, such as fibrinogen and high-molecular-weight kininogen. The biological activities of tryptase and chymase from rat may be regulated by their dissociation from and association with trypstatin, an endogenous inhibitor of these proteases.     

The Clinical and Laboratory Studies of Superoxide Dismutase Activity in the Human Whole Blood with Early Gastric Cancer

In this study, we tried to evaluate the usefulness of Superoxide Dismutase (SOD) activity in detecting gastric cancer. SOD was determined according to M. Minami and H. Yoshikawa. a simple and inexpensive assay method. For II fibrognstroscopy and pathological proved gastric cancer cases, the average levels of SOD activity was found significantly lower than 30 patients with gastric diseases, 8 patients with atypical hyperplasia and 32 controls.     

Human Pluripotent Stem Cell-Derived Tumor Model Uncovers the Embryonic Stem Cell Signature as a Key Driver in Atypical Teratoid/Rhabdoid Tumor

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Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks

E. K. J. Risse, J. P. Holierhoek, E. M. Meijer‐Marres, E. Ouwerkerk‐Noordam and M. E. Boon Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks Objective: The purpose of this study was to reduce the number of diagnoses of atypical glandular cells (AGC). Residual material from the cervical ThinPrep® samples (Hologic, Marlboruogh, MA, USA) was used for cell blocks (CB) and immunohistochemistry (IHC). Methods: In 2007 there were 87 patients (0.12% of tests) with AGC on liquid‐based cytology (LBC) in the Leiden Cytology and Pathology Laboratory (LCPL) using the Bethesda System 2001 (TBS). CB with IHC was used for 26 of these cases. The vials still containing the brush (Cervex‐Brush^® Combi) were placed in a shaker for 10 minutes to dislodge the material trapped between the bristles. The residual sampling fluid was used to prepare paraffin sections (Shandon Cytoblock^®) stained with Papanicolaou and immunostaining. Results: Four of five cases with AGC not otherwise specified (NOS) were diagnosed with CB/IHC as benign mimics (endometrium, tubal metaplasia, follicular cervicitis, microglandular hyperplasia) and one of four with AGC‐favour neoplasia (FN) (endocervical polyp). In one of five cases with AGC‐NOS and in two of seven with AGC‐FN, CIN3 was found on subsequent histological biopsy. Of six cases diagnosed as adenocarcinoma in situ (AIS) on LBC with CB/IHC the diagnosis was confirmed in four; one was adenocarcinoma and one glandular atypia. Of eight cases diagnosed as adenocarcinoma on cytology and CB/IHC, the diagnosis was confirmed in three. The other five cases were found to be one each of AIS, squamous cell carcinoma, CIN3, CIN2 with glandular atypia, and cervical endometriosis. Conclusions: By reducing the number of benign mimics of AGC, we achieved a high proportion (16/26; 61.5%) of neoplastic or preneoplastic lesions (glandular or squamous) on histological outcome potentially avoiding colposcopy. Histological biopsy verification by the gynaecologist is needed for final diagnosis of AGC‐FN, AIS and adenocarcinoma.     

Emerging Roles and Research Tools of Atypical Ubiquitination

Ubiquitination is a posttranslational modification characterized by the covalent attachment of ubiquitin molecules to protein substrates. The ubiquitination modification process is reversible, dynamic, and involved in the regulation of various biological processes, such as autophagy, inflammatory responses, and DNA damage responses. The forms of ubiquitin modification are very diverse, incorporating either a single ubiquitin molecule or a complicated ubiquitin polymer, and different types of ubiquitination usually elicit corresponding cellular responses. The development of research tools and strategies has afforded more detailed insight into atypical ubiquitin signaling pathways that were previously poorly understood. Here, an update on the understanding of atypical ubiquitin chain signaling pathways is provided and the recent development of representative research tools for ubiquitin systems is discussed. In addition, the future challenges in ubiquitin research are reflected on and summarized.     

Studies on the susceptibility of different culture morphotypes of Listeria monocytogenes to uptake and survival in human polymorphonuclear leukocytes

This study demonstrated that atypical virulent filaments of Listeria monocytogenes (rough variant type II and designated FR for this study), isolated from clinical specimens or generated during exposure to pulsed-plasma gas discharge in liquids, were shown to be capable of survival when engulfed by human polymorphonuclear leukocytes (PMNLs). Factors shown to significantly influence the maximal respiratory burst response in PMNLs and survival of different internalized cell or filament forms of L. monocytogenes were bacterial strain, culture form, degree of opsonization (with and without the use of 10% serum) and composition of the bacterial growth media used before uptake by PMNLs. Opsonized regular-sized L. monocytogenes cells grown on blood agar (BA) elicited the greatest respiratory burst response and survived best in PMNLs. The filamentous (FR) and multiple cell chain (MCR) rough variants were significantly less susceptible to uptake and survival in PMNLs. Supplementation of tryptone soya agar with hemin resulted in significantly reduced chemiluminescence responses in phagocytosing PMNLs compared with the maximal levels observed from prior bacterial growth on BA or brain heart infusion agar that also contained a source of iron. The MCR variants secreting decreased levels of a peptidoglycan hydrolase CwhA protein exhibited the lowest percentage survival when internalized in PMNLs compared with wild-type smooth or FR culture variants as determined by the macrophage-killing assay.