Pitfalls of insulin pump clocks: technical glitches that may potentially affect medical care in patients with diabetes.

The objective was to raise awareness about the importance of ensuring that insulin pumps internal clocks are set up correctly at all times. This is a very important safety issue because all commercially available insulin pumps are not GPS-enabled (though this is controversial), nor equipped with automatically adjusting internal clocks. Special attention is paid to how basal and bolus dose errors can be introduced by daylight savings time changes, travel across time zones, and am-pm clock errors.

Noninvasive respiratory support in the perioperative period.

Purpose Of Review: Pulmonary complications ranging from atelectasis to acute respiratory failure are common causes of poor perioperative outcomes. As the surgical population becomes increasingly at risk for pulmonary dysfunction due to increasing age and weight, development of an approach toward respiratory compromise in these patients is becoming ever more important. Given the utility of noninvasive respiratory support (NRS) in acute respiratory failure, it is likewise likely to also be important in the perioperative period.

Critical care organ support: a focus on extracorporeal systems.

Purpose Of Review: An extensive search of the literature published in the past 2 years related to critical care organ support was undertaken. This review is limited to those that focus on extracorporeal life support modalities for adults.

Recent Findings: Traditional indications for extracorporeal life support such as oxygenation, carbon dioxide exchange and support of perfusion have expanded to include solute and toxin clearance for kidney, liver and potentially neurological failure.

CD4+ T cells recognizing a single self-peptide expressed by APCs induce spontaneous autoimmune arthritis.

We have examined processes leading to the spontaneous development of autoimmune inflammatory arthritis in transgenic mice containing CD4+ T cells targeted to a nominal Ag (hemagglutinin (HA)) and coexpressing HA driven by a MHC class II promoter. Despite being subjected to multiple tolerance mechanisms, autoreactive CD4+ T cells accumulate in the periphery of these mice and promote systemic proinflammatory cytokine production. The majority of mice spontaneously develop inflammatory arthritis, which is accompanied by an enhanced regional immune response in lymph nodes draining major joints.

Rapid preparation of high-quality frozen sections using a membrane and vacuum system embedding machine.

Background: A wide variety of embedding techniques have been employed to process frozen sections for Mohs micrographic surgery. Prospective data comparing different techniques are lacking.

Objective: The purpose of this study was to compare tissue processing times and slide quality using the three embedding techniques.

B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection.

Acute allograft rejection requires the activation of alloreactive CD4 T cells. Despite the capacity of B cells to act as potent APCs capable of activating CD4 T cells in vivo, their role in the progression of acute allograft rejection was unclear. To determine the contribution of B cell APC function in alloimmunity, we engineered mice with a targeted deficiency of MHC class II-mediated Ag presentation confined to the B cell compartment.

Cutting edge: impaired transitional B cell production and selection in the nonobese diabetic mouse.

Developing B cells undergo selection at multiple checkpoints to eliminate autoreactive clones. We analyzed B cell kinetics in the NOD mouse to establish whether these checkpoints are intact. Our results show that although bone marrow production is normal in NOD mice, transitional (TR) B cell production collapses at 3 wk of age, reflecting a lack of successful immature B cell migration to the periphery.

The frequency of double-positive thymocytes expressing an alphabeta TCR clonotype regulates peripheral CD4 T cell compartment homeostasis.

The present study aimed to determine whether the frequency of double positive (DP) thymocytes expressing alphabeta T-cell receptor (TCR) clonotypes at the time of selection regulates peripheral CD4 T-cell compartment size. Scid recipients were inoculated with various ratios of TCR Calpha(0/0) and wild-type bone marrow (BM) stem cells. Increasing the frequency of TCR Calpha(0/0) thymocytes at steady-state introduced a graded decrease in the maturation probability of the total DP thymocyte pool.

Specificity-based negative selection of autoreactive B cells during memory formation.

Autoreactive B cells are not completely purged from the primary B cell repertoire, and whether they can be prevented from maturation into memory B cells has been uncertain. We show here that a population of B cells that dominates primary immune responses of BALB/c mice to influenza virus A/PR/8/34 hemagglutinin (HA) are negatively selected in transgenic mice expressing PR8 HA as an abundant membrane-bound Ag (HACII mice). However, a separate population of B cells that contains precursors of memory B cells is activated by PR8 virus immunization and is subsequently negatively selected during the formation of the memory response.

Alloreactive CD4 T cell activation in vivo: an autonomous function of the indirect pathway of alloantigen presentation.

Activation of alloreactive CD4 T cells occurs via the direct and indirect pathways of alloantigen presentation. A novel TCR/alloantigen transgenic system was designed that permitted in vivo visualization of CD4 T cell priming through these pathways. When both pathways of alloantigen presentation were intact, CD4 T cell activation in response to cardiac allografts was rapid and systemic by day 4 after transplantation, in contrast to that seen in response to skin allografts, which was delayed until 10-12 days after transplantation.

The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells.

Autoreactive B cells that appear to be inactivated can be found in healthy individuals. In this study, we examined the potential of these anergic cells to become activated. We show that anergy of anti-double-stranded DNA (dsDNA) B cells in BALB/c mice is readily reversed, requiring only the provision of T cell help.