Requirement of the expression of 3-phosphoglycerate dehydrogenase for traversing S phase in murine T lymphocytes following immobilized anti-CD3 activation.

Murine resting (G(0)) T lymphocytes contained no detectable mRNA of 3-phosphoglycerate dehydrogenase (PHGDH) catalyzing the first step in the phosphorylated pathway of l-serine biosynthesis. Immobilized anti-CD3 activation of G(0) T cells expressed the PHGDH mRNA in G(1) with a maximum level in S phase. G(0) T cells activated with either immobilized anti-CD3 plus CsA or PBu(2), which failed to drive the activated T cells to enter S phase, did not express the PHGDH mRNA unless exogenous rIL-2 was added.

Enhanced Aβ(1-40) production in endothelial cells stimulated with fibrillar Aβ(1-42).

Amyloid accumulation in the brain of Alzheimer's patients results from altered processing of the 39- to 43-amino acid amyloid β protein (Aβ). The mechanisms for the elevated amyloid (Aβ(1-42)) are considered to be over-expression of the amyloid precursor protein (APP), enhanced cleavage of APP to Aβ, and decreased clearance of Aβ from the central nervous system (CNS). We report herein studies of Aβ stimulated effects on endothelial cells.

Multiparameter flow cytometry for discovery of disease mechanisms in rheumatic diseases.

Flow cytometry has emerged as an essential tool for investigators in the study of the complexity of the immune system and the examination of its role in human health and disease. This technology has developed to the point where one can readily generate a large descriptive data set that details the levels of important immune cell subsets and defines an individual immune cell signature or “Immune-cellome”. This immune cell signature would clearly display individual variation but also would change in a manner reflective of disease state.

Late stage erythroid precursor production is impaired in mice with chronic inflammation.

Background: We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active.

Design And Methods: We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice.

Transcription of proteinase 3 and related myelopoiesis genes in peripheral blood mononuclear cells of patients with active Wegener's granulomatosis.

Objective: Wegener's granulomatosis (WG) is a systemic inflammatory disease that is associated with substantial morbidity. The aim of this study was to understand the biology underlying WG and to discover markers of disease activity that would be useful for prognosis and treatment guidance.

Methods: Gene expression profiling was performed using total RNA from peripheral blood mononuclear cells (PBMCs) and granulocyte fractions from 41 patients with WG and 23 healthy control subjects.