Evaluation of immunotoxic and immunodisruptive effects of inorganic arsenite on human monocytes/macrophages

A trivalent inorganic arsenic, arsenite, has been causing chronic inflammation in humans through the consumption of contaminated well water. The total peripheral blood arsenic concentrations of chronic arsenic-exposed patients, who had inflammatory-like immune responses, are less than 1 microM, thus, nM concentrations may be very important regarding the chronic inflammatory effects by arsenite. However, there are few reports about the biological effects of low concentrations of arsenite in mammalian cells, especially in normal immune effector cells. In this study, we examined whether arsenite has any biological and/or toxicological effects on the differentiation of human peripheral blood monocytes into macrophages using the colony-stimulating factor (CSF) in vitro compared with that of other metallic compounds, and found that arsenite sensitively inhibited the CSF-induced in vitro maturation of monocytes into macrophages at nM levels, and it also induced small, nonadhesive and CD14-positive abnormal macrophage generation from monocytes with granulocyte-macrophage CSF (GM-CSF) at 50-500 nM without cell death. The addition of other metallic compounds, including chromium, selenium, mercury, cadmium, nickel, copper, zinc, cobalt, manganese and other human pentavalent arsenic metabolites, such as inorganic arsenate, monomethylarsonic acid and dimethylarsinic acid, could not induce the same abnormal cell generation from monocytes with CSFs at any concentration and any additional time schedules; they showed only simple cytolethality in monocytes and macrophages at n-mM levels accompanied by cell death. This work may have implications in the arsenic-induced chronic inflammation in humans.     

Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.     

Familial inclusion body myositis: a report on two Japanese sisters

Familial occurrence of inclusion body myositis is extremely rare, and only a few cases in Western countries have been reported. In these reports, a strong association of this disease with DR3 (DRB1*0301/0302) and the efficacy of immunosuppressants suggested that an immune pathomechanism is involved in the disease. We, for the first time, report two Japanese sisters who suffered myopathy clinicopathologically similar to inclusion body myositis. One sister received corticosteroid and azathioprine and the therapy relieved dysphagia. Both of our patients had DR15(2)/4 (DRB1*1502/0405), suggesting a distinct genetic association with the disease in the Japanese population.     

Left out: immigrants' access to health care and insurance

Recent policy changes have limited immigrants' access to insurance and to health care. Fewer noncitizen immigrants and their children (even U.S.-born) have Medicaid or job-based insurance, and many more are uninsured than is the case with native citizens or children of citizens. Noncitizens and their children also have worse access to both regular ambulatory and emergency care, even when insured. Immigration status is an important component of racial and ethnic disparities in insurance coverage and access to care.     

High prevalence of HCV infection among the general population in a rural area of central Italy

The hepatitis C virus infection (HCV) is the most frequent cause of hepatic infection in Europe. In Italy, anti-HCV positivity values are extremely variable, depending on the age and geographic location of the population being analysed. The aims of the study were: (1) evaluating positivity for anti-HCV antibodies in various age groups and determining the HBsAg in a mountainous and predominantly farming area in central Italy; (2) assessing some anamnestic and clinical variables through a questionnaire, submitted during the taking of blood samples, in order to determine HCV exposure and risk factors for the target population. 344 subjects selected by random sampling among 3308 people, older than 16, were considered as the target population. A prevalence study was carried out. The sources of data were: blood samples taken to carry out the HCV positivity test; a questionnaire including items about exposures at risk and case-historical and clinical patient data. The risk of infection was evaluated by a multiple logistic regression model. The inferred HCV+ prevalence rate is 22.4/100 (95% confidence interval (CI): 20.8–24.1). An increasing age trend is shown with a higher positive predominance among females (28.99/100 vs. 14.29/100 in males). The positive HBsAg prevalence in the examined survey is 1.2/100. Variables associated with the HCV occurrence are case history of pneumonopathy (OR: 4.9) and exposure to parenteral therapies with glass syringes (OR: 3.3). This study is consistent with literature about the hypothesis of a north-south geographic gradient in the hepatitis C occurrence in Italy. Data clearly show the effects of the inappropriate use of medical or surgery practices on the population, with particular reference to the use of glass syringes. No elements prove that the farming features of the area may be predictive of HCV infection risk. The extent of the recorded prevalence values calls for the implementation of programmes aimed at detecting clusters or population areas at risk.     

Three cases of gastrointestinal stromal tumor (GIST) with bone metastasis]

We report three cases of gastrointestinal stromal tumor (GIST) with delayed bone metastasis at least four years after initial surgery. One small intestinal and two rectal GISTs were all considered as high-risk according to the classification based on tumor size and mitotic count. GIST usually metastasizes to the liver and peritoneum, however bone metastasis should be considered in the patients with long prognosis.     

Shape of Barrett��s epithelium is associated with prevalence of erosive esophagitis

AIM: To test the hypothesis that the shape and length of Barrett’s epithelium are associated with prevalence of erosive esophagitis.METHODS: A total study population comprised 869 patients who underwent endoscopy during a health checkup at our hospital. The presence and extent of Barrett’s epithelium were diagnosed based on the Prague C & M Criteria. We originally classified cases of Barrett’s epithelium into two types based on its shape, namely, flame-like and lotus-like Barrett’s epithelium, and into two groups based on its length, its C extent < 2 cm, and ≥ 2 cm. Correlation of shape and length of Barrett’s epithelium with erosive esophagitis was examined.RESULTS: Barrett’s epithelium was diagnosed in 374 cases (43%). Most of these were diagnosed as short-segment Barrett’s epithelium. The prevalence of erosive esophagitis was significantly higher in subjects with flame-like than lotus-like Barrett’s epithelium, and in those with a C extent of ≥ 2 cm than < 2 cm.CONCLUSION: Flame-like rather than lotus-like Barrett’s epithelium, and Barrett’s epithelium with a longer segment were more strongly associated with erosive esophagitis.     

Potential association of prolonged patient interval and advanced anatomic stage in breast cancer patients in the area affected by the 2011 triple disaster in Fukushima,Japan: Retrospective observational study

For five years after the 2011 triple disaster (earthquake, tsunami, and nuclear disaster) in Japan, the proportion of patients with undiagnosed symptomatic breast cancer remained elevated in the coastal area of Fukushima. These individuals experienced a prolonged interval from first symptom recognition to initial medical consultation (hereafter referred to as the patient interval). We aimed to investigate how this prolonged patient interval affected disease staging.Using patient records, we retrospectively extracted females with newly and pathologically diagnosed breast cancer who initially presented to Minamisoma Municipal General Hospital from March 2011 to March 2016. We estimated the proportion with advanced-stage disease (III, IV) according to the patient interval duration (<3 months, 3–12 months, and 12 months plus). A cut-off patient interval value was determined based on the previous evidence with regards to impacts on survival prospects. Logistic regression approaches were used to fulfill the study outcome.The proportion of patients with advanced-stage disease was 10.3% for < 3 months (7/68), 18.2% for 3–12 months (2/11), and 66.7% for more than 12 months (12/18). We found a similar trend using the multivariate logistic regression analyses.Prolongation of the patient interval was associated with advanced-stage disease among female patients with breast cancer.