Increment of serum bilirubin as an independent marker predicting new-onset type 2 diabetes mellitus in a Korean population.

BACKGROUND AND AIMS: Several cross-sectional studies reported that serum bilirubin concentrations had an inverse association with type 2 diabetes mellitus (T2DM) prevalence. The aim of the current study was to investigate the relationship between percentage change in bilirubin levels (PCB) and incident risk of T2DM using a longitudinal model. METHODS AND RESULTS: 22,084 participants who received regular health check-ups between 2006 and 2012 were enrolled. Multivariable-adjusted Cox regression models were used to determine the hazard ratio (HR) of incident T2DM based on PCB. PCB was determined by subtracting baseline serum bilirubin level (BB) from the bilirubin level at the end of follow-up or a year before the last date of diagnosis, dividing by BB and multiplying by 100. Compared to non-diabetics, BB was lower in the diabetic group at the initial visit. There were 20,098 participants without T2DM at the initial visit; 1253 new cases occurred during follow-up. As PCB increased, T2DM incidence also increased (P < 0.001). After adjusting for confounders, the HR of incident T2DM in the highest PCB quartile was 2.08 (95% confidence interval [CI] 1.76-2.46). This trend remained significant when PCB was analyzed as a continuous variable (HR for 1-SD increment, 1.25; 95% CI 1.19-1.31). Additional analysis comparing the rate of PCB during the follow-up period revealed that the serum bilirubin level of the Incident T2DM group increased before T2DM development and decreased rapidly thereafter compared to others (P < 0.001). CONCLUSIONS: Bilirubin level increment over time is associated with T2DM development.

Stimulation of epidermal calcium gradient loss increases the expression of hyaluronan and CD44 in mouse skin.

BACKGROUND: Hyaluronan (HA), a major extracellular matrix component in epidermis, has been found to accumulate in the epidermis after disruption of the epidermal barrier; however, the precise mechanisms underlying this process are not yet clear. Alterations in the epidermal calcium gradient are an important signal for permeability-barrier homeostasis. Thus, we hypothesized that epidermal calcium-ions might regulate HA expression. AIM: To investigate whether changes in the epidermal calcium gradient and subsequent induction of cytokines regulate HA, HA synthase (HAS) and HA receptor (CD44) expression in mouse epidermis, and to clarify the mechanisms of HA induction. METHODS: Sonophoresis of 1.5 mmol/L Ca(2+)-containing gel or Ca(2+)-free gel was performed to manipulate the epidermal Ca(2+) content without disrupting the permeability barrier. We also manipulated the Ca(2+) gradient by tape-stripping with or without 2 h immersion in 1.2 mmol/L Ca(2+)-containing solutions. Next we inhibited cytokine activity using tumour necrosis factor (TNF)-alpha or interleukin (IL)-1 inhibitors before sonophoresis. Six hours after each treatment, the expression of HA, HAS and CD44 were analysed using reverse transcription PCR and immunohistochemical stains. RESULTS: Sonophoresis of Ca(2+)-free gel significantly increased HA, HAS3 and CD44 expression in epidermis and in tape-stripped skin. However, the inhibition of Ca(2+) decrease in the upper epidermis by sonophoresis of Ca(2+)-containing gel or immersion of barrier-disrupted skin into a Ca(2+)-containing solution attenuated these inductions. Specific inhibitors of TNF-alpha and IL-1 specific inhibitors also abolished the sonophoresis-induced expression of HA, HAS3 and CD44. CONCLUSIONS: These results suggest that modulations in epidermal calcium regulate HA and CD44 expression directly or via induction of cytokines.

Entry of B cell receptor into signaling domains is inhibited in tolerant B cells.

Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling in autoreactive B cells, a transgenic model was used to isolate a homogeneous population of tolerant B lymphocytes. These cells were compared with a similar population of naive B lymphocytes. We show that the BCR from naive B cells enters a detergent-insoluble domain of the cell within 6 s after antigen binding, before a detectable increase in BCR phosphorylation. This fraction appears to be important for signaling because it is enriched for lyn kinase but lacks CD45 tyrosine phosphatase and because the BCR that moves into this domain becomes more highly phosphorylated. Partitioning of the BCR into this fraction is unaffected by src family kinase inhibition. Tolerant B cells do not efficiently partition the BCR into the detergent-insoluble domain, providing an explanation for their reduced tyrosine kinase activation and calcium flux in response to antigen. These results identify an early, regulated step in antigen receptor signaling and self-tolerance.

Thallium-201 uptake in keloid tissue masquerading as a pulmonary neoplasm.

Tl-201 imaging is useful in the diagnostic work-up of tumors. However, Tl-201 uptake is not specific for tumor and is also noted in other conditions. A case is described in which Tl-201 was taken up by a keloid.

Changes in spectral indices of heart rate variability during exercise in acute myocardial infarction.

Physical exertions are related to sudden cardiac death following acute myocardial infarction (AMI). Abnormalities in the autonomic modulation during exercise were noted in animals with AMI that were susceptible to potentially lethal arrhythmias. This study was done to evaluate the changes in the autonomic activity during exercise and recovery in AMI patients with good exercise capacity, using spectral analysis of R-R intervals of electrocardiogram (ECG). Symptom-limited treadmill exercise test was done on 17 patients of AMI with mild heart failure (in 7-10 days after the attack) and 21 healthy controls. The exercise was divided into 7 stages; rest, early exercise, mid-exercise, peak exercise, early recovery, mid-recovery, and late recovery. Power spectral analysis of R-R intervals of ECG was performed for each stage. Low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) powers, and their ratio were obtained. These parameters were observed throughout the stages in both groups. The trend of their changes during exercise and recovery was essentially the same for both groups; high and low frequency powers progressively decreased during exercise and abruptly increased during early recovery, but did not return to the values at those of rest until 9 minutes into the recovery. When the parameters were compared between the groups, there was a significantly greater decrease of high frequency power during the early exercise (p < 0.05), and a higher ratio of low to high frequency power during the early recovery (p < 0.05) in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)