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.     

Diagnosis of Small Pancreatic Carcinoma

A retrospective analysis was performed to evaluate the clinicalsymptoms and abnormal test findings in small pancreatic carcinoma.Five hundred and thirty-six cases of pancreatic carcinoma withthe histology of duct cell carcinoma were collected from 14medical centers in Japan. In 440 of the cases, tumor size wasmeasured at the time of laparotomy or from the resected specimen.Three hundred and seventy-seven patients (86%) had a carcinomalarger than 3.0 cm; only 30% of these were resectable. Sixty-threepatients (14%) had a carcinoma of 3.0 cm or less, with resectabilityof 97%. Detecting a tumor of "3 cm or less" with a high probabilityof resectability is the objective of early diagnosis with theresulting possibility of a cure. In most cases these small carcinomaswere found easily when obstructive jaundice was present (73%).However, the estimated occurrence of obstructive jaundice associatedwith carcinomas of 3 cm or less was only 10% among the totalcases of pancreatic carcinoma studied. Therefore, it is necessaryfor early diagnosis to detect carcinomas of 3 cm or less presentingwithout jaundice. The symptoms of small carcinoma without jaundiceare weight loss, anorexia, upper abdominal pain, back pain anda palpable abdominal mass. Among the various available examinations,endoscopic retrograde cholangiopancreatography, computerizedtomography and ultrasonography were valuable in diagnosing thesesmall carcinomas.     

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.     

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.     

Morphological comparison and functional reconstitution of rat hepatic parenchymal cells on various matrices

Four types of materials, type I collagen coat (Coat), acid-soluble type I collagen gel (Hardgel), pepsin-treated acid-soluble type I collagen gel (Softgel), and an extract of extracellular matrix of the murine Engelbreth-Holm-Swarm sarcoma (Matrigel), were used as matrices to culture rat hepatic parenchymal cells, and their morphological changes and adhesion were compared to the matrices by electron microscopic observations. Hepatic parenchymal cells cultured on Coat and Hardgel were extended and flattened, whereas cells cultured on Softgel and Matrigel assembled and formed aggregates. Such aggregates consisted of several hepatic parenchymal cells, with a recognizable bile duct-like alveolus on the inside. Morphologically, the aggregates were more spherical on Matrigel and oval shaped on Softgel. Microvilli of the cell surface were parallel to the matrix on Matrigel, but invaded into the gel on Softgel. Subsequently, investigation into how these morphological features affected the liver-specific functions, including secretion of albumin and induction of P450 by 3-methylcholanthrene, demonstrated that a high level of liver function was maintained in a long-term culture in hepatic parenchymal cells on Softgel. These results suggest that hepatic parenchymal cell interactions were stronger with Softgel than with Matrigel, and that Softgel appears to closely mimic the in vivo environment.     

PREVALENCE OF RAYNAUD'S PHENOMENON AND SPECIFIC CLINICAL SIGNS RELATED TO PROGRESSIVE SYSTEMIC SCLEROSIS IN THE GENERAL POPULATION OF JAPAN

Background. In order to evaluate the prevalence rates of Raynaud's phenomenon (RP) and specific clinical signs related to progressive systemic sclerosis (PSS) in the general population of Japan, inquiries were made concerning RP in the hands and dermatologic examinations were also conducted. Methods. One thousand and sixty-three subjects (332 men and 731 women) over 30 years of age who underwent inhabitants' health examinations in 1990 were considered for this study. Results. The prevalence of RP was 3.0% in men and 3.4% in women. In 8 men and 17 women with RP who received the blood tests, the positive rates of antinuclear antibody (ANA) were 12.5% and 35.3% in men and women, respectively. The prevalence rates of all five specific clinical signs related to PSS, sclerodactyly, pitting scars of the fingers, brown pigmentation of the body, shortened frenulum of the tongue, and flexion contracture of fingers, were under 2% in men and 3% in women. In women with RP the prevalence rates of sclerodactyly, pitting scars of the fingertips, brown pigmentation of the body, and shortened frenulum of the tongue were 16.0, 4.0, 4.0, and 16.0%, respectively. These values were significantly higher than those of persons without RP. Conclusions. Because some persons with primary RP may become typical cases of PSS within several years, a follow-up study, particulary for women who have positive titers of ANA with RP, should be carried out to find out whether the persons suffer from PSS or not.     

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.     

Surveillance interval of endoscopic examinations for colorectal cancer screening

Background: There have been a few evidence‐based studies concerning the relationship between the length of the surveillance interval of colonoscopic examinations and the risk of colorectal cancer (CRC). The aim of the present study was to assess the appropriate interval between endoscopic examinations for CRC screening in a retrospective cohort study. Methods: The cohort included subjects in whom cancer was not detected at the initial endoscopic examination and in whom endoscopic examination(s) was subsequently performed one or more times. The results of the endoscopic examinations performed in the mass screening for CRC between November 1983 and March 1999 were analyzed. The study end point was the detection of CRC and the detection rates of cancer were assessed among those who underwent examinations at various intervals between successive endoscopic examinations. Results: Among the 117 636 cohort subjects, 63 invasive cancer cases and 112 mucosal cancer cases were found. The odds ratio (OR) for invasive cancer was not significantly elevated even when the interval between successive examinations was over 5 years. The OR for mucosal or invasive cancer was significantly elevated among the subjects in whom the interval between successive examinations was over 5 years (OR, 1.71; 95% confidence interval (CI), 1.07–2.73), than among those in whom the interval was 1 year. Conclusions: Since prolongation of the interval between endoscopic examinations of up to 5 years did not result in any change in the cancer risk among persons who are at average risk for CRC, 5 years may be an adequate interval between endoscopic examinations in the mass screening for CRC.