The microbial product lipopolysaccharide confers diabetogenic potential on the T cell repertoire of BDC2.5/NOD mice: implications for the etiology of autoimmune diabetes

Both genetic predisposition and environmental factors participate in the etiology of Type-1 diabetes. To test the role of the microbial product lipopolysaccharide (LPS) as an environmental trigger of autoimmune diabetes, we employed transgenic (tg) BDC2.5/NOD mice that bear an islet-specific CD4(+) T cell repertoire (>95%), but do not develop the spontaneous diabetes that typifies the NOD (nonobese diabetic) strain. LPS administration provoked diabetes in BDC2.5/NOD mice by their 16th week of age. However, LPS administration in NOD mice did not accelerate their diabetes. This finding indicates that the frequency of islet-specific T cells influences LPS-mediated diabetes. Furthermore, in vitro LPS-cultured splenocytes from BDC2. 5/NOD and BDC2.5-microMT (B-cell-deficient) mice effectively transferred diabetes into immunodeficient NOD-scid/scid mice but not immunosufficient NOD mice. Therefore, B lymphocytes are not required for LPS-provoked autoimmune diabetes. Flow cytometric analysis then revealed that LPS-stimulation in vitro induced the expression of an IL-2 receptor (CD25) on CD4 T cells; this indicates that the activation of islet-specific T cells is a prerequisite to eliciting diabetes in this situation. Overall, these results point to microbial LPS as an etiopathogenic agent of autoimmune diabetes.     

Emergencies in Patients With Inherited Hemoglobin Disorders—An Emergency Department Perspective

In the ED, the inherited Hb disorders may be encountered in a variety of clinical presentations. Patients with the clinically milder forms of hemoglobinopathies are typically identified as having these disorders only as an incidental finding as they usually do not present to the ED for hemoglobinopathy-related issues. In contrast, patients with the more severe forms of these disorders tend to present with symptoms that are more or less directly related to their hemoglobinopathy. Examples include signs of severe hemolysis and signs of anemia in the case of the thalassemia disorders, or hemolysis, anemia, sepsis, vasoocclusion, and specific organ-related complications in the case of SCD. These presentations usually require immediate interventions to prevent morbidity and mortality. Alternatively, these patients may also present with symptoms related to chronic organ damage from either the disease itself or from its treatment such as long-term blood transfusions, which can result in iron overload, heart failure, liver cirrhosis, and diabetes secondary to pancreatic insufficiency. A basic knowledge of the pathophysiology of these disorders and a good index of suspicion are necessary for the diagnosis and appropriate management of children affected by these disorders.     

Quercetin Attenuates Benzo(α)pyrene-induced CYP1A Expression

<正>We studied effects of nutrient quercetin on cytochromes’Р450 1А(CYP1A)activities(measured spectrofluorimetrically using 7-ethoxy-resorufin for CYP1A1 and 7-methoxy-resorufin for CYP1A2 as substrates),on mR NA levels(measured by RT-PCR),and on DNA-binding activities(evaluated by an electrophoretic mobility shift assay)of proteins regulating CYP1A expression in untreated and benzo(α)pyrene(Ba P)-treated rats.Wistar rats