Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema

The expression of two autoimmune thyroid diseases, GD and idiopathic myxoedema, is associated with antibodies to the thyroid-stimulating hormone (TSH) receptor. Thyroid stimulating antibodies (TSAb) in GD are TSH agonists and cause hyperthyroidism as well as goitre, whereas thyroid stimulation blocking antibodies (TSBAb) in idiopathic myxoedema are TSH antagonists and cause hypothyroidism and thyroid atrophy. We investigated the effect of antibodies to TSH receptor on Fas-mediated apoptosis of thyroid epithelial cells (thyrocytes). Human IgG was isolated from healthy donors, patients with GD and idiopathic myxoedema. Human thyrocytes were obtained from surgical specimens. Thyrocytes were cultured in the presence or absence of human IgG with or without interferon-gamma (IFN-γ) or IL-1β for a specified time. After incubation, we examined the level of cAMP in cultured supernatants and both Fas and Bcl-2 expression on thyrocytes. In addition, we examined anti-Fas-mediated apoptosis of thyrocytes. Fas expression on thyrocytes was significantly down-regulated by Graves' IgG and TSH, although idiopathic myxoedema IgG did not affect Fas expression on thyrocytes. Idiopathic myxoedema IgG abrogated the effect of TSH on both cAMP production and inhibition of Fas expression on thyrocytes. Treatment of thyrocytes with IL-1β or IFN-γ caused a marked augmentation of Fas expression on thyrocytes. The increase of Fas expression of thyrocytes induced by IL-1β or IFN-γ was significantly suppressed in the presence of TSH or Graves' IgG. Anti-Fas-induced apoptosis of thyrocytes was observed in thyrocytes treated with IL-1β or IFN-γ, but was markedly inhibited in the presence of TSH or Graves' IgG. Furthermore, idiopathic myxoedema IgG abrogated most of the inhibitory effect of TSH on Fas-mediated apoptosis of thyrocytes treated with IL-1β or IFN-γ. Bcl-2 expression of thyrocytes did not change after stimulation with TSH, Graves' IgG, idiopathic myxoedema IgG, IL-1β or IFN-γ. These results suggest that TSAb found in Graves' patients may be potentially involved in the development of goitre by inhibition of Fas-mediated apoptosis of thyrocytes. In addition, TSBAb inhibit the action of TSH and increase the sensitivity toward Fas-mediated apoptosis of thyrocytes, inducing thyroid atrophy seen in patients with idiopathic myxoedema.     

A Case of Pneumocytoma (So-Called Sclerosing Hemangioma) With Lymph Node Metastasis

A case of "sclerosing hemangionia" (pneumocytoma) of the lungwith lymph node metastasis is reported. A 22-year-old Japaneseman was found to have a well-defined round lesion in the rightlung (S⁷), which increased in size slightly during a 2-yearfollow-up period. He underwent right lower lobectomy with a preoperative diagnosisof a benign lung tumor. The pulmonary tumor revealed histologicalfeatures characteristic of "sclerosing hemangioma" of the lung,in addition to which there were many large polygonal foamy cells,forming tubular or papillary structures. These cells were foundby electron microscopy to contain numerous cytoplasmic lamellarbodies and showed a positive reaction with anti-surfactant apoproteinantibody immunohistochemically. Therefore, they were consideredto be cells differentiating toward type II pneumocytes. Reviewof 21 typical "sclerosing hemangionia" disclosed a few or somesuch foamy cells in 10 cases. A single hilar lymph node wasthe site of microscopic metastases, which consisted of "largeclear foamy cells" and smaller polygonal or round cells withslightly eosinophilic cytoplasm, both of which were componentsof the pulmonary "sclerosing hemangioma" This case supportsthe theory that "sclerosing hemangioma" is a neoplasm of typeII pneumocyte lineage. Although it is said to be benign, rarecases apparently show metastatic potential.     

Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): Familiarization Using Cyclophosphamide

Combined Repeat Dose and Reproductive/Developmental ToxicityScreening Test (OECD): Familiarization Using Cyclophosphamide.TANAKA, S., KAWASHIMA, K., NAITO, K., USAMI, M., NAKADATE, M.,IMAIDA, K., TAKAHASHI, M., HAYASHI, Y., KUROKAWA, Y., AND TOBE,M. (1992A, Y., AND TOBE, M. (1992). Fundam. Appl. Toxicol. 18,89–95. A familiarization study was conducted on the "Combined RepeatDose and Reproductive/Developmental Toxicity Screening Test(ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at dosesof 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavageto groups of 12 male and 12 female Sprague-Dawley rats. As aresult, anemia and leukopenia were evident in treated males.The absolute and relative thymus and spleen weights were decreasedin treated rats. Histopathologically, atrophy of the thymus,spleen, and bone marrow was observed. With respect to the reproductive/developmentaltoxicity, dose-dependent increases in postimplantation lossof fetuses and postnatal death were found in dams given CP.The body weight of pups treated with CP was significantly loweredin a dose-related manner. Thus the results demonstrated mostof the known toxicological properties of CP, except the adverseeffects on spermatogenesis and fertility. Therefore ReproToxcan be considered as a useful screening test for assessing repeatdose and reproductive/developmental toxicity of existing chemicalsof high production volume.     

Job Demands,Job Resources,and Job Performance in Japanese Workers: A Cross-sectional Study

This study investigated the cross-sectional association of job demands (i.e., psychological demands) and job resources (i.e., decision latitude, supervisor support, co-worker support, and extrinsic reward) with job performance. A total of 1,198 workers (458 males and 740 females) from a manufacturing company in Japan completed a self-administered questionnaire that included the Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, World Health Organization Health and Work Performance Questionnaire, and demographic survey. Hierarchical multiple regression analyses were conducted. After adjusting for demographic characteristics, decision latitude (β=0.107, p=0.001) and extrinsic reward (β=0.158, p<0.001) were positively and significantly associated with job performance while supervisor support (β=−0.102, p=0.002) was negatively and significantly associated with job performance. On the other hand, psychological demands or co-worker support was not significantly associated with job performance. These findings suggest that higher decision latitude and extrinsic reward enhance job performance among Japanese employees.     

Development of a Short Version of the New Brief Job Stress Questionnaire

This study was aimed to investigate the test-retest reliability and validity of a short version of the New Brief Job Stress Questionnaire (New BJSQ) whose scales have one item selected from a standard version. Based on the results from an anonymous web-based questionnaire of occupational health staffs and personnel/labor staffs, we selected higher-priority scales from the standard version. After selecting one item with highest item-total correlation coefficient from each scale, a 23-item questionnaire was developed. A nationally representative survey was administered to Japanese employees (n=1,633) to examine test-retest reliability and validity. Most scales (or items) showed modest but adequate levels of test-retest reliability (r>0.50). Furthermore, job demands and job resources scales (or items) were associated with mental and physical stress reactions while job resources scales (or items) were also associated with positive outcomes. These findings provided a piece of evidence that the short version of the New BJSQ is reliable and valid.     

Aqueous fraction of Sauropus androgynus might be responsible for bronchiolitis obliterans

Background and objective: Bronchiolitis obliterans (BO) has been reported to develop following ingestion of Sauropus androgynus (SA), a leafy shrub distributed in Southeast Asia. Little is known about direct effects of SA on airway resident cells or haematopoietic cells in vitro. Identification of the SA component responsible for the development of BO would be an important key to elucidate its mechanism. We sought to elucidate the direct effects of SA on airway resident cells or haematopoietic cells and identify the SA element responsible for the pathogenesis of BO. Methods: SA dry powder was partitioned into fractions by solvent extraction. Human and murine monocytic cells, epithelial cells and endothelial cells were cultured with SA solution or fractions eluted from SA. We also investigated the effect of SA in vivo using a murine BO syndrome (BOS) model. Results: The aqueous fraction of SA induced significant increases of inflammatory cytokine and chemokine production from monocytic lineage cells. This fraction also induced significant apoptosis of endothelial cells and enhanced intraluminal obstructive fibrosis in allogeneic trachea allograft in the murine BOS model. We found individual differences in tumour necrosis factor α (TNF‐α) production from monocytes of healthy controls stimulated by this aqueous fraction of SA, whereas it induced high‐level TNF‐α production from monocytes of patients with SA‐induced BO. Conclusions: These results suggest that an aqueous fraction of SA may be responsible for the pathogenesis of BO.     

Acute childhood leukemia in a patient with hemophilia: First report in Japan

This study reports an unusual case of acute leukemia which was diagnosed as hemophilia A on initial admission for leukemia. A 3 year old boy was admitted to Kagoshima University Hospital with anemia. He was diagnosed as acute lymphoblastic leukemia. At the same time he was revealed to have severe hemophilia A⁻ without any previous episodes of severe bleeding tendency or family history of this disease. The laboratory investigation showed his mother to be a carrier of hemophilia A. Although there are many cases of hemophilia which have developed malignant tumors, most of them were caused by association with human immunodeficiency virus (HIV) infection. Only five cases with coexistence of leukemia and hemophilia without HIV infection have been reported and the present case is the first one in Japan. At this stage, hemophiliacs are not necessarily regarded to be a population at risk for the development of leukemia. Furthermore, no particular subtype of leukemia was characterized among these patients in the literature.     

Effects of Nonanal,trans-2-Nonenal and 4-Hydroxy-2,3-trans-nonenal on Cyclooxygenase and 12-Lipoxygenase Metabolism of Arachidonic Acid in Rabbit Platelets

The effects of nonanal, trans-2-nonenal and 4-hydroxy-2,3-trans-nonenal on the formation of thromboxane B₂ (TXB₂), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid in washed rabbit platelets were examined. Nonanal and trans-2-nonenal at concentrations ranging from 0.25 to 2 μm inhibited TXB₂, HHT and 12-HETE formation, reducing the amounts of these three arachidonic acid metabolites by 50% at nonanal and trans-2-nonenal concentrations of approximately 0.25 μm. The inhibition of TXB₂, HHT and 12-HETE formation induced by 4-hydroxy-2,3-trans-nonenal (50% inhibition by 4-hydroxy-2,3-trans-nonenal at a concentration of approximately 100 μm) was 400 times weaker than that induced by nonanal and trans-2-nonenal. These results suggest that nonanal and trans-2-nonenal can be modulators of platelet arachidonic acid metabolism by affecting the activity of cyclooxygenase and 12-lipoxygenase.     

The influence of physical restraint or fasting on plaque-forming cell response in mice

Abstract This study was designed to investigate the effects of 1- and 3-day (16 h/day) physically restrained or fasting on immunological and endocrine responses in CBF1 mice. The influence of stressors on these responses was evaluated using anti-sheep red blood cell plaque-forming assay, and by examining T cell subsets, thymus weight and endocrine hormone levels. The results revealed that a significant elevation of the plaque-forming cells (PFC) was found in spleen cells in 1-day restrained mice, that the PFC were conversely suppressed following 3-day physically restrained stress, and that the PFC were not affected by 1- or 3-day fasting stress. Serum levels of norepinephrine were found to be significantly increased only in 1-day physically restrained mice. No change of T cell subsets and thymus weight was found in 1-day physically restrained mice. A significant increase in serum corticosterone levels was elicited in both 1- and 3-day physically restrained mice, and 3-day fasting mice, while increased Lyt2-positive T cells and thymic atrophy were found only in 3-day physically restrained mice. These findings suggest that immune function was differentially affected by the duration and types of stressors.     

Resetting of Tachycardia Cycle by Single and Double Ventricular Extrastimuli in Recurrent Sustained Ventricular Tachycardia

In two cases with recurrent sustained ventricular tachycardia (VT) due to re-entry, the response pattern to extrastimuli during the tachycardia was studied. In each case, right ventricular extrastimuli with longer coupling intervals during VT were followed by fully compensatory pauses and with shorter coupling intervals reset the tachycardia cycle. In one case, a plateau was produced by a single extrastimulus, resembling that seen in the response curve of sinus node automaticity as well as ectopic atrial tachycardia. Two successive stimuli produced three definite zones, i.e., fully compensatory, reset producing a plateau, and progressive prolongation zones with shortening of the coupling intervals between the two stimuli, and terminated the tachycardia with further shortening of the coupling intervals. In conclusion, resetting phenomenon was confirmed on two cases with re-entrant VT. This phenomenon cannot be used as a criterion to determine the mechanism responsible for VT.