Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

Background: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF.

Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy.

Linkage analysis of the dominant distal myopathy we previously identified in a large Australian family demonstrated one significant linkage region located on chromosome 7 and encompassing 18.6 Mbp and 151 genes. The strongest candidate gene was FLNC because filamin C, the encoded protein, is muscle-specific and associated with myofibrillar myopathy.

Expression of cardiac alpha-actin spares extraocular muscles in skeletal muscle alpha-actin diseases--quantification of striated alpha-actins by MRM-mass spectrometry.

As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle alpha-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac alpha-actin, the alpha-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac alpha-actin in the extraocular muscles of human, pig and sheep to those in the heart.

Congenital myopathies.

Purpose Of Review: The aim of this review is to provide an up-to-date personal analysis of current congenital myopathy research.

Recent Findings: In the past year novel congenital myopathies have been suggested, genes have been discovered for some of the congenital myopathies for the first time (beta-tropomyosin in cap disease and perhaps skeletal muscle alpha-actin in Zebra body myopathy), further genes have been identified for congenital myopathies where other genes had already been found (cofilin in nemaline myopathy, selenoprotein N in congenital fibre type disproportion) and recessive myosin storage myopathy was associated with homozygous mutation of slow-skeletal/beta-cardiac myosin which was already known to be mutated in dominant myosin storage myopathy. There has been further clarification of the pathobiology of the congenital myopathies, including determination of the basis of epigenetic effects: silencing of the normal allele in recessive central core disease and persistence of cardiac (fetal) alpha-actin in nemaline myopathy patients with no skeletal actin.

The impact of respiratory syncytial virus infection on endothelin receptor function and release in sheep bronchial explants.

We investigated the impact of respiratory syncytial virus (RSV) infection, an important asthma precipitant, on endothelin receptor function and release in sheep bronchial explants. RSV infection was confirmed using polymerase chain reaction and immunohistochemistry. Since sheep airway smooth muscle contains only endothelin-A receptors, sarafotoxin (Stx) S6c did not cause airway contraction.

Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus.

Objectives: The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B-48 and apoC-III concentrations in postmenopausal women with and without type 2 DM.

Patients: Twenty-four postmenopausal women without DM and 14 postmenopausal women with diet-controlled DM of similar age and body mass index (BMI) were studied in the postabsorptive state.

Comparison of nitration and oxidation of tyrosine in advanced human carotid plaque proteins.

The importance of reactive nitrogen species in atherosclerosis remains poorly understood, despite the semi-quantitative evidence for the presence of 3-nitrotyrosine provided by immunohistochemical staining studies. At this time, there appear to be no data describing the prevalence of nitration relative to oxidation in atherosclerotic plaque proteins. The present study used 3-nitrotyrosine and dityrosine as markers of nitration and oxidation respectively to examine the relative abundance of each process.

Evidence for the nitration of gamma-tocopherol in vivo: 5-nitro-gamma-tocopherol is elevated in the plasma of subjects with coronary heart disease.

This study investigated the hypothesis that nitration of gamma-tocopherol may be an important mechanism for the detoxification of reactive nitrogen oxide species in vivo. Using liquid chromatography-tandem MS we have shown that gamma-tocopherol can be nitrated in vivo to form 5-nitro-gamma-tocopherol and that concentrations of this compound are elevated in the plasma of subjects with coronary heart disease. In addition, we demonstrate in carotid-artery atherosclerotic plaque that nitration of gamma-tocopherol is also evident at levels similar to that seen in the plasma of subjects with coronary heart disease.

Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse.

Hereditary hemochromatosis (HH) is a disorder of iron metabolism in which enhanced iron absorption of dietary iron causes increased iron accumulation in the liver, heart, and pancreas. Most individuals with HH are homozygous for a C282Y mutation in the HFE gene. The function of HFE protein is unknown, but it is hypothesized that it acts in association with beta(2)-microglobulin and transferrin receptor 1 to regulate iron uptake from plasma transferrin by the duodenum, the proposed mechanism by which body iron levels are sensed.

Crystallization and preliminary X-ray analysis of the complex of the epsilon-subunit and the central domain of the gamma-subunit from the Escherichia coli ATP synthase.

A complex of the epsilon-subunit and the central domain of the gamma-subunit from the ATP synthase of Escherichia coli has been purified and crystallized and preliminary X-ray analysis has been carried out. The crystals belong to space group C222(1), with unit-cell parameters a = 76.7, b = 176.

Structure of the gamma-epsilon complex of ATP synthase.

ATP synthases (F(1)F(o)-ATPases) use energy released by the movement of protons down a transmembrane electrochemical gradient to drive the synthesis of ATP, the universal biological energy currency. Proton flow through F(o) drives rotation of a ring of c-subunits and a complex of the gamma and epsilon-subunits, causing cyclical conformational changes in F(1) that are required for catalysis. The crystal structure of a large portion of F(1) has been resolved.