Anaplastic astrocytoma with eosinophilic granular cells

A 68‐year‐old man, who had no remarkable past medical history, was referred to a hospital because of disorientation and right‐sided hemiparesis. On magnetic resonance imaging, a contrast‐enhanced tumor in the left frontal lobe with perifocal edema was noted. He underwent left frontal lobectomy. Microscopic examination revealed infiltrative atypical astrocytes showing increased cellularity, distinct nuclear atypia, and many mitotic figures, while microvascular proliferation and necrosis were absent. Thus, the tumor was histologically diagnosed as anaplastic astrocytoma. It was of note that cytoplasmic eosinophilic granules were observed in approximately 25% of neoplastic cells. The granules were positively immunostained with anti‐αB‐crystallin antibody, and the other histochemical and immunohistochemical results also corresponded to Rosenthal fibers. The MIB‐1 labeling index of the highest area of the tumor was 22%, while that of granular cells was 2.1%. An ultrastructural study revealed amorphous electron‐dense structures attached to intermediate filament bundles, compatible with Rosenthal fibers. Such structures are relatively common in oligodendroglial tumors; however, they are extremely rare in astrocytic tumors. Fluorescence in situ hybridization targeted against chromosome 1 failed to demonstrate allelic loss of the short arm. The present case should also be discriminated from granular cell astrocytoma. We review related literature and discuss the significance of granules in gliomas.     

Werner Syndrome

Werner syndrome is a premature aging disease caused by the mutation in the WRN gene. The cloning andcharacterization of the WRN gene and its product allows investigators to study the disease and the human aging process atmolecular level. This review summarizes the recent progresses on various aspects of the WRN research including functionalanalysis of the protein, interactive cloning, complexes formation, mouse models, and SNPs (single nucleotidepolymorphisms). These in depth investigations have greatly advanced our understanding of the disease and elucidated futureresearch direction for Werner syndrome and the human aging process.     

Colchicine-induced Inhibition of Fat Globule Development in Hepatocytes of Rats Injected with Ethionine

To examine the effect of colchicine on ethionine induced fatty liver, adult female rats were starved overnight and then injected i.p. with 1 g kg ethionine at 11th hour of fasting; then a half of the rats were also injected i.p. with 2.5 mg kg colchicine twice at 3 and 6 h after the single administration of ethionine. Similarly, fasted control rats were injected i.p. with vehicle alone at the above times. All of the rats were sacrificed after a 20 h fast, and the hepatocytes in periportal areas were observed ultra-structurally. In addition, total lipids in the liver tissue were extracted and determined biochemically. Although similar significant increases of triglyceride were observed in the liver tissue of all ethionine-injected rats, the hapatocytes in the group treated with both chemicals had fewer cytoplasmic fat globules (CFG) than those in the group treated with ethionine only. On the other hand, the diameters of markedly increased membrane-bound lipid particles (MLP) in the double treated group were distributed mainly in the range 0.2–0.4 μm, compared with those (0.1-0.2 μm) in the other groups. These findings indicate that colchicine inhibits the development of CFG in ethionine injured hapatocytes. Acta Pathol Jpn 39: 281∼288, 1989.     

Immature dendritic cells (CD11c+ CD3- B220- cells) present in mouse peripheral blood

It is well known that dendritic cells (DCs) are developed from the peripheral blood of mice when peripheral blood mononuclear cells (PBMCs) are cultured with GM-CSF. We have previously found that immature DCs are present in the blood even in humans. In the present study, we show that CD11c+ CD3- B220- cells in the mouse peripheral blood are immature DCs. The percentage of CD11c+ CD3- B220- cells in the (PBMCs) of normal mice ranges from 0.5 to 2.5%. The CD11c+ CD3- B220- cells in the PBMCs show dendrites, similar in shape to the CD11c+ CD3- B220- cells in the spleen, which are thought to be DCs definitely. However, they have practically no capacity to stimulate the proliferation of allogeneic T cells, and show a lower expression of MHC class II, B7-1 and B7-2 than CD11c+ CD3- B220- cells in the spleen. When the CD11c+ CD3- B220- cells in the PBMCs are cultured with GM-CSF, they show not only the potent ability to stimulate the proliferation of allogeneic T cells but also a higher expression of MHC class II, B7-1 and B7-2. Moreover, they migrate into the spleen when they are injected intravenously. These results suggest that CD11c+ CD3- B220- cells in the PBMCs are immature DCs, and that they migrate into the spleen, where they mature.     

C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-beta production

We here report a molecular basis for downregulation of interferon (IFN)-beta production by V and C proteins of Sendai virus (SeV). The infection of HeLa cells with SeV poorly induced IFN-beta even if the expression of C/C' was disrupted. In contrast, when the expression of C/C'/Y1/Y2 or V/W was disrupted, SeV infection strongly induced IFN-beta production and significantly activated the interferon regulatory factor (IRF)-3 pathway. The independent expression of C or V inhibited the double-stranded (ds) RNA- or Newcastle disease virus (NDV)-induced activation of IRF-3 and NF-kappa B, as well as the IFN-beta promoter. This inhibitory effect was also observed when Y1, Y2, or a C-terminal half fragment (aa 85-204) of C was independently expressed. Phosphorylation and homodimer formation of IRF-3 were suppressed not only in cells infected with SeV capable of expressing both C/C'/Y1/Y2 (or Y1/Y2) and V/W, but also in HeLa cells constitutively expressing Y1. These results suggest that C, Y1, Y2, and V block signaling pathways leading to IRF-3 activation to downregulate IFN-beta production.     

Validation of ECRHS Questionnaire in Japanese to use for nation-wide prevalence study of adult asthma]

PURPOSE: To enable international comparison of prevalence in asthma, we translated and evaluated ECRHS Questionnaire, which is introduced in GINA. Considering COPD prevalence in elder people, we added two questions to the ECRHS Questionnaire. METHOD: The Japanese edition of ECRHS Questionnaire was responded by 366 patients who were diagnosed asthma without COPD, 61 patients who were diagnosed COPD without asthma, and 137 healthy persons who were not diagnosed asthma or COPD. We analyzed the answers of the each group and evaluated the validity of the questionnaire to use for the nation-wide prevalence study of adult asthma in future. RESULTS: The question of 'Wheezing at any time in the last 12 months' had the highest Youden's index and validity to pick up asthma patients. The questions of 'Waking up with a feeling of tightness in chest at any time in the last 12 months' and 'Waking up by an attack of shortness of breath at any time in the last 12 month' had the highest specificity to pick up asthma patients. Most of the questions which were related asthma were able to be answered by asthma patients properly, but some questions were improperly answered by patients and healthy persons in elderly. The results in this study showed the less recognition of their diseases in elderly patients than younger patients and the limitation of the study with written questionnaire for elderly people. Not a few COPD patients complained wheezing or whistling in the chests as same as asthma patients in this study. CONCLUSION: We concluded that we had almost enough reliability in the Japanese edition of the ECRHS questionnaire for screening survey of asthma prevalence in Japan.     

Therapy with nebulized beta2 agonists (procaterol) in asthmatic children: pulmonary function and plasma levels after inhalation]

BACKGROUND: Relationship between post administrative changes in plasma drug levels and bronchodilation remains unknown. In this study, we measured plasma levels of procaterol, a beta2-agonist, when being inhaled through nebulizers in children with bronchial asthma to examine relationship between improvement of pulmonary function and the plasma levels. METHOD: Six asthmatic children with the mean age of 9.8 years, inhaled 0.3 ml of 0.01% procaterol solution through a nebulizer. We examined changes in pulmonary function and plasma procaterol levels before and after inhalation. RESULTS: Procaterol was detected in the plasma 2 minutes after inhalation when it already rose to the maximum level, and kept the steady until showing a decline in 30 minutes. The measured highest value was 87.8+/-45.1 pg/ml. FEV 1.0 remarkably increased 2 minutes after inhalation and was maintained until 60 minutes after inhalation. Other lung function parameters also improved. There was no significant change in the heart rate, but serum potassium concentrations significantly dropped in all patients 60 minutes after inhalation. CONCLUSION: Plasma procaterol levels promptly rose to the peak at 2 minutes after inhalation and decreased 30 minutes later. Improvement of pulmonary function started promptly at minutes after inhalation and it became a peak 60 minutes later.