No abstract

We have attempted to elucidate an involvement of cathepsin E (CE) in major histocompatibility complex class II-mediated antigen presentation by microglia. In primary cultured murine microglia, CE was localized mainly in early endosomes and its expression level was markedly increased upon stimulation with interferon-␥. Pepstatin A, a specific inhibitor of aspartic proteases, significantly inhibited interleukin-2 production from an OVA-(266 -281)-specific T helper cell hybridomas upon stimulation with native OVA presented by interferon-␥-treated microglia. However, pepstatin A failed to inhibit the presentation of OVA-(266 -281) peptide. The possible involvement of CE in the processing of native OVA into antigenic peptide was further substantiated by that digested fragments of native OVA by CE could be recognized by OVA-specific Th cells. Cathepsin D also degraded native OVA into antigenic peptide, whereas microglia prepared from cathepsin D-deficient mice retained an ability for antigen presentation. On the other hand, the requirement for cysteine proteases such as cathepsins S and B in the processing of invariant chain (Ii) was confirmed by immunoblot analyses in the presence of their specific inhibitors. In conclusion, CE is required for the generation of an antigenic epitope from OVA but not for the processing of Ii in microglia.

BACKGROUND AND PURPOSE:Previous studies have suggested that use of an artificial neural network (ANN) system is beneficial for radiological diagnosis. Our purposes in this study were to construct an ANN for the differential diagnosis of intra-axial cerebral tumors on MR images and to evaluate the effect of ANN outputs on radiologists' diagnostic performance.

The kinetics of changes in Toxoplasma gondii abundance were evaluated with a quantitative competitive (QC)-polymerase chain reaction (PCR) assay at various sites in both C57BL/6 and BALB/c mice. Higher mortality was apparent in C57BL/6 mice than in BALB/c mice when infected with a high dose of cysts. There were significant differences in cyst number when infected with a low dose of cysts, although there was no significant difference in mortality between the 2 mouse strains. One day after infection with a low dose of an avirulent Fukaya strain, T. gondii was detected in peripheral blood, mesenteric lymph nodes, spleen, lungs, and brain. Two weeks after infection, the number of T. gondii in the brain greatly increased in C57BL/6 mice but not in BALB/c mice. Thus, it would appear that the first to second week after infection is a critical period in determining T. gondii abundance. QC PCR allows the detection of low numbers of T. gondii at an early stage of infection in the murine model. This is useful for the early diagnosis of toxoplasmosis and to understand reactivation of toxoplasmosis.

ObjectiveWe aimed to clarify the onset of diabetes.DesignData from 27,392 nondiabetic health examinees were retrospectively analyzed for a mean of 5.3 years. Trajectories of fasting plasma glucose (FPG), body mass index (BMI), and the single point insulin sensitivity (Si) estimator (SPISE), an index of Si, 10 years before diagnosis of prediabetes (PDM; n = 4781) or diabetes (n = 1061) were separately assessed by a mixed effects model. Diabetes and PDM were diagnosed by the American Diabetes Association definition on the basis of FPG and glycosylated hemoglobin A1c values.ResultsIn individuals who developed diabetes, mean FPG and BMI were significantly higher (P < 0.01 each) and SPISE lower than those who did not at −10 years: FPG 101.5 mg/dL vs 94.5 mg/dL, BMI 24.0 kg/m2 vs 22.7 kg/m2, and SPISE 7.32 vs 8.34, P < 0.01 each. These measurements, in subjects who developed prediabetes, were slightly but definitely different from those who did not, already at −10 years: FPG 91.8 mg/dL vs 89.6 mg/dL, BMI 22.6 kg/m2 vs 22.1 kg/m2, and SPISE 8.44 vs 8.82, P < 0.01 each. In both cases, the differences were progressively greater toward year 0, the time of diabetes, or PDM diagnosis.ConclusionsFPG was significantly elevated in those who developed diabetes at least 10 years before diagnosis of diabetes, and this was also the case in those who developed PDM. Glucose dysregulation precedes diagnosis of diabetes at least for 20 years.