Morphological evidence of exocrine function in coagulating gland renin of mouse strain C57BL/6

Background: Renin is classically secreted from juxtaglomerular cells of the kidney by endocrine or paracrine mechanisms. In a previous report, intense renin immunoreactivity was observed in the coagulating gland (CG), a new source for renin in mice. In the present study, immunoelectron microscopical analysis for renin was carried out to clarify the secretory site of CGs. Methods: Five adult male C57BL/6 mice were used in this study. The CGs were fixed with an ice-cold 2% glutaraldehyde and 2% paraformaldehyde mixture and embedded in Lowicryl K4M. Ultrathin sections were treated with antimouse renin antiserum and colloidal gold (15 nm)-labeled protein A complex. Results: In immunoelectron microscopical observation, renin was first detected at the Golgi vacuoles just budding from the lamellae, although it was not demonstrated in all Golgi vacuoles. In the production series of exocrine granules, renin immunoreactivity was observed in some granules that were distributed in the supranuclear region. Both renin-positive and negative exocrine granules were secreted from the apical cell membrane by exocytosis. The lysosomal granules also showed stronger renin immunoreactivity and contained homogeneous or heterogeneous materials. In the supranuclear region, it was observed that exocrine granules were fused with irregular lysosomal granules. At the apical region, such lysosomal granules were closely associated with cell membrane. At the basolateral region, immunoreactivity for renin was localized in electron dense granules. Conclusions: These results suggest that part of the renin in the CGs is released by exocrine secretion into the genital tract. © 1995 Wiley-Liss, Inc.     

Combined effect of a direct oral anticoagulant edoxaban and an inhibitor of activated thrombin-activatable fibrinolysis inhibitor on clot lysis

Journal of Thrombosis and Thrombolysis - Fibrinolysis is regulated by the thrombin/thrombin-activatable fibrinolysis inhibitor (TAFI) system. Thus, anticoagulants and inhibitors of TAFI are...     

Early stage clear cell adenocarcinoma of the colon examined in detail with image-enhanced endoscopy: a case report

Primary clear cell adenocarcinoma (CCA) of the colorectum is a rare tumor. We report on a 48-year-old man with early stage CCA in the descending colon who underwent detailed examination with image-enhanced endoscopy, such as magnifying endoscopy with narrow-band imaging and crystal violet staining. The tumor was treated successfully with endoscopic mucosal resection at our hospital.     

Evaluation of systemic inflammatory responses in neonates with herpes simplex virus infection

Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity. To investigate the pathogenesis of neonatal HSV infection, we examined inflammatory responses and markers of apoptosis in patients with neonatal HSV infection. Concentrations of inflammatory cytokines and markers of apoptosis were significantly higher in patients with disseminated HSV infection and were correlated with HSV load. It appears that the immunopathological damage that results from host responses to viral infection leads to organ dysfunction in patients with neonatal HSV infection.     

Corticosteroids in the treatment of the acute phase of Kawasaki disease.

OBJECTIVES: Corticosteroids are considered to be contraindicated during the acute phase of Kawasaki disease (KD) based on unfavorable results in early studies. In our hospital, however, corticosteroids have been used in some cases of KD with satisfactory results. We analyzed outcomes of patients with KD treated with or without corticosteroids. STUDY DESIGN: Medical records of 299 children with KD treated with one of the 4 regimens were reviewed retrospectively. Regimen 1 consisted of aspirin, dipyridamole, and propranolol; regimen 2 was regimen 1 plus prednisolone, 2 mg/kg/d, for 1 week, followed by tapering over 2 weeks; regimen 3 was regimen 1 plus intravenous gamma-globulin (IVGG), 200 or 400 mg/kg/d, for 5 consecutive days; and regimen 4 was regimen 1 plus both prednisolone and IVGG. RESULTS: Although patients treated with regimens 2 and 4 were more ill at presentation than those treated with regimens 1 and 3, respectively, the duration of fever was shorter in the former patient groups (P =.0013). Coronary aneurysms developed least frequently in patients treated with regimen 4 and less frequently with regimen 2 than with regimen 1 (P =.0730). Multiple regression analysis showed significant reductions of fever and coronary aneurysm incidence with prednisolone (P <.0001 and P =.0307, respectively). CONCLUSION: Our data suggest a possible role of corticosteroids in the treatment of the acute phase of KD.     

Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type

Natural killer (NK) cell lymphomas/leukemias are highly aggressive lymphoid malignancies, but little is known about their genomic alterations, and thus there is an urgent need for identification and analysis of NK cell lymphomas/leukemias. Recently, we developed our own array-based comparative genomic hybridization (array CGH) with an average resolution of 1.3 Mb. We performed an array CGH analysis for 27 NK-cell lymphoma/leukemia cases that were classified into two disease groups based on the World Health Organization Classification (10 aggressive NK-cell leukemia cases and 17 extranodal NK/T-cell [NK/T] lymphomas, nasal type). We identified the differences in the genomic alteration patterns of the two groups. The recurrent regions characteristic of the aggressive NK-cell leukemia group compared with those of the extranodal NK/T lymphoma, nasal-type group, were gain of 1q and loss of 7p15.1-p22.3 and 17p13.1. In particular, gain of 1q23.1-24.2 (P = 0.041) and 1q31.3-q44 (P = 0.003-0.047), and loss of 7p15.1-p22.3 (P = 0.012-0.041) and 17p13.1 (P = 0.012) occurred significantly more frequently in the former than in the latter group. Recurrent regions characteristic of the extranodal NK/T lymphoma, nasal-type group, compared with those of the other group were gain of 2q, and loss of 6q16.1-q27, 11q22.3-q23.3, 5p14.1-p14.3, 5q34-q35.3, 1p36.23-p36.33, 2p16.1-p16.3, 4q12, and 4q31.3-q32.1. Our results can be expected to provide further insights into the genetic basis of lymphomagenesis and the clinicopathologic features of NK-cell lymphomas/leukemias.     

Knowledge-assisted recognition of cluster boundaries in gene expression data

BACKGROUND AND MOTIVATION: DNA microarray technology has made it possible to determine the expression levels of thousands of genes in parallel under multiple experimental conditions. Genome-wide analyses using DNA microarrays make a great contribution to the exploration of the dynamic state of genetic networks, and further lead to the development of new disease diagnosis technologies. An important step in the analysis of gene expression data is to classify genes with similar expression patterns into the same groups. To this end, hierarchical clustering algorithms have been widely used. Major advantages of hierarchical clustering algorithms are that investigators do not need to specify the number of clusters in advance and results are presented visually in the form of a dendrogram. However, since traditional hierarchical clustering methods simply provide results on the statistical characteristics of expression data, biological interpretations of the resulting clusters are not easy, and it requires laborious tasks to unveil hidden biological processes regulated by members in the clusters. Therefore, it has been a very difficult routine for experts. OBJECTIVE: Here, we propose a novel algorithm in which cluster boundaries are determined by referring to functional annotations stored in genome databases. MATERIALS AND METHODS: The algorithm first performs hierarchical clustering of gene expression profiles. Then, the cluster boundaries are determined by the Variance Inflation Factor among the Gene Function Vectors, which represents distributions of gene functions in each cluster. Our algorithm automatically specifies a cutoff that leads to functionally independent agglomerations of genes on the dendrogram derived from similarities among gene expression patterns. Finally, each cluster is annotated according to dominant gene functions within the respective cluster. RESULTS AND CONCLUSIONS: In this paper, we apply our algorithm to two gene expression datasets related to cell cycle and cold stress response in budding yeast Saccharomyces cerevisiae. As a result, we show that the algorithm enables us to recognize cluster boundaries characterizing fundamental biological processes such as the Early G1, Late G1, S, G2 and M phases in cell cycles, and also provides novel annotation information that has not been obtained by traditional hierarchical clustering methods. In addition, using formal cluster validity indices, high validity of our algorithm is verified by the comparison through other popular clustering algorithms, K-means, self-organizing map and AutoClass.     

Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide

To clarify the essential role of NKT cells in allergy, we investigated the contribution of NKT cells to the pathogenesis of eosinophilic airway inflammation using alpha-galactosylceramide (alpha-GalCer), a selective ligand for NKT cells. Although continuous administration of alpha-GalCer during ovalbumin (OVA) sensitization increased OVA-specific IgE levels and worsened eosinophil inflammation, a single administration of alpha-GalCer at the time of OVA challenge completely prevented eosinophilic infiltration in wild-type mice. This inhibitory effect of alpha-GalCer was associated with a decrease in airway hyperresponsiveness, an increase in IFN-gamma, and decreases in IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluids. Analysis of lung lymphocytes revealed that production of IFN-gamma increased in NK cells, but not in T or NKT cells, following alpha-GalCer administration. Induction of vascular cell adhesion molecule-1 in the lungs of wild-type mice was also significantly attenuated by treatment with alpha-GalCer. These effects of alpha-GalCer were abrogated in J alpha281-/- mice, which lack NKT cells, and in wild-type mice treated with anti-IFN-gamma Ab. Hence, our data indicate that alpha-GalCer suppresses allergen-induced eosinophilic airway inflammation, possibly by inducing a Th1 bias that results in inhibition of eosinophil adhesion to the lung vessels.