Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

OBJECTIVE: A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. METHODS: Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. RESULTS: Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P < 0.01) increased in SLE patients by LC-MS/MS. Three G3BP-exposing microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. CONCLUSIONS: Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of immune complexes occurring in lupus nephritis.

Circulating microparticles and plasma levels of soluble E- and P-selectins in patients with systemic sclerosis.

OBJECTIVES: Microparticles (MPs) may be involved in the pathogenesis of systemic sclerosis (SSc), which includes vasculopathy, endothelial cell activation, and coagulation activation. Circulating MPs from SSc patients were characterized and their relationship with soluble markers of vascular activation investigated. METHOD: This study included 121 SSc patients [79 with limited (lcSSc) and 42 with diffuse cutaneous SSc (dcSSc)] and 49 sex- and age-matched healthy controls (HCs). The MPs were characterized by flow cytometry for annexin V (AnxV)-binding capacity and their expression of surface markers of platelets (PMPs), leucocytes (LMPs), or endothelial cells (EMPs). Plasma levels of soluble (s) E- and P-selectins were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The total concentrations of MPs and of PMPs, LMPs, and EMPs were 22-42% lower in SSc patients than in HCs (p < 0.001). However, within the cell-derived MP pool, a 47% higher fraction of AnxV non-binding MPs (F-AnxV(-) MPs) was found in the SSc patients compared to the HCs (p < 0.05). The plasma levels of sE- and sP-selectins were increased by 47-64% in the SSc patients compared to HCs (p < 0.001). Multiple regression analysis showed that the raised plasma levels of sE- and sP-selectin were associated with F-AnxV(-) EMPs in dcSSc patients (p = 0.008 and p = 0.001, respectively) but not in lcSSc patients (p = 0.33 and p = 0.82, respectively). CONCLUSIONS: While the total number of MPs was decreased, the number of F-AnxV(-) MPs increased in SSc patients. The F-AnxV(-) EMPs were associated with plasma levels of markers of vascular activation in patients with dcSSc.

Aspects of the barley seed proteome during development and germination.

Analysis of the water-soluble barley seed proteome has led to the identification of proteins by MS in the major spots on two-dimensional gels covering the pI ranges 4-7 and 6-11. This provides the basis for in-depth studies of proteome changes during seed development and germination, tissue-specific proteomes, cultivar differences related to quality parameters, analysis of the genetic basis for spot variations and targeted investigations of specific proteins.

[Peroperative radiologic findings of axillary lymph nodes in breast cancer]. / Peroperativ radiologisk påvisning af aksillymfeknuder ved cancer mammae.

The series consists of 49 operable breast cancers, prospectively registered over a five month period. The removed axillary fat was peroperatively radiologically examined by trained radiologist, and the result was reported to the surgeon. Afterwards it was sent to the pathologist for a thorough histopathological examination. Peroperative radiographic examination showed that 30.6% of the resected axillary fat contained less than ten lymph nodes. Subsequent pathological examination found that only 8.2% actually contained less than ten lymph nodes. We conclude that peroperative radiological examination of removed axillary fat is not a reliable method to assess the number of lymph nodes removed during the surgical procedure. In our hands, a careful anatomical dissection removing all axillary fatty tissue and lymphatics including level I and II seems to be the method of choice.

Felodipine in addition to beta-adrenergic blockade for angina pectoris. a multicentre, randomized, placebo-controlled trial.

The additional efficacy, duration of action and tolerability of felodipine were evaluated in patients with stable angina pectoris and a positive stress test who were already receiving therapy with a beta-adrenergic blocker. One hundred and twenty-eight patients were randomized to double-blind treatment with 5-10 mg felodipine once daily or matching placebo, and were evaluated by serial exercise testing during 12 weeks of treatment. Felodipine at 4 h significantly increased exercise duration assessed after 4 weeks of treatment (increase 34 +/- 65 s vs 18 +/- 71 s in placebo-treated patients; 95% confidence interval 1.01-1.11; P = 0.01), and after 12 weeks of treatment (increase 39 +/- 103 s vs 3 +/- 72 s; 95% confidence interval 1.01-1.16; P = 0.02). The time until onset of exercise-induced anginal pain and time until 1 mm ST depression assessed after 4 weeks of treatment also increased significantly with felodipine compared to placebo. No statistically significant changes in exercise test parameters evaluated 24 h after medication were observed. The addition of felodipine once daily demonstrated a sustained improvement in exercise duration in patients symptomatic despite treatment with a beta-blocker evaluated 4 h after drug intake. At 24 h post dose, no statistically significant effect was observed. Felodipine is well tolerated with a low incidence of side-effects and no adverse effect on quality of life.

Evaluation of the ulcerogenic effect of potassium chloride by endoscopy and fecal blood loss.

In a blinded-observer crossover study, 16 volunteers ingested equimolar doses of three different potassium chloride preparations and placebo for nine days in a random order. The irritating effect on the mucosa was evaluated by means of upper gastrointestinal endoscopy and fecal blood loss, measured by reference to the amount of radioactivity in three 24-hour samples after previous injection of 51Cr-tagged autologous red cells. The microencapsulated KCl capsule preparation induced three ulcers, but the total endoscopic group score was not significantly higher than the score with placebo. The total endoscopic group score for the wax-matrix formulation was significantly higher than the score for placebo (P less than .05) and for a new microencapsulated KCl tablet preparation containing a potent disintegrant (P less than .10). We did not find any significant differences in mean fecal blood loss during the four different treatments. A correlation between endoscopic score and fecal blood loss was found in the placebo group (r = .54) and the microencapsulated KCl capsule preparation (r = .56) group.

Plasma exchange in the treatment of propoxyphene intoxications.

Six patients heavily intoxicated by propoxyphene were treated with plasma exchange. Only one patient died because of cardiac dysrhythmia, the other five patients survived, probably because the plasma exchange removed the free plasma fraction of propoxyphene. Plasma exchange also proved to be effective in improving the consciousness of the patients.