ABSTRACT
The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic β-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on “gene-environment interactions” in the development of a reduced pancreatic β-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic β-cells, ultimately resulting in the development of pancreatic β-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic β-cell failure as revealed by previous reports and data from experiments.
ABSTRACT
Three patients with hypersensitivity pneumonitis caused by inhalation of spores of Cortinus shiitake (Lentinus edodes) cultivated in vinyl houses were observed. These three patients developed the disease after harvesting shiitake for several hours in closed frame houses with a heater in the autum and winter. The frames were full of spores of shiitake and the patients suffered from a discordant feeling, systemic weakness, a feeling of cold, fever (over 38 C), a feeling of airway occlusion, a slight cough and sputum. These symptoms disappeared during rest the next day.<BR>Case 1 was examined by the inhalation provocation test with a suspension of shiitake spores and spore-allergen. This test caused several clinical symptoms (fever, airway occlusion and various symptomatic feelings), leucocytosis, decrease of PaO<SUB>2</SUB> a positive reaction of CRP and X-ray findings (appearance of interstitial pneumonitis shadows).<BR>The 3 patients were considered to be suffering from allergic hypersensitivity pneumonitis due to inhalation of spores of Cortinus shiitake, because of their work, the development of symptoms after work in specific occupational conditions, a positive reaction to precipitating antibody against spore-allergen of shiitake, negative reactions to precipitation antibodies to 11 molds-allergens, various abnormal values in immunological tests and a positive reaction in a provocation test in one case.<BR>In a survey of 45 shiitake-grower, it was found that 6 (13.3%) suffered from respiratory disease. No difference was found in the incidence of intracutaneous reactions to spore-allergen or allergen of dried shiitake in non-farm workers. Among 31 growers of shiitake a precipitation antibody to spore-allergen was observed only in these three patients. These results indicate that an allergic disposition is very important for development of hypersensitivity pneumonitis.