Effects of the chemokine MIP-1alpha on anemia and inflammation in rheumatoid arthritis

Macrophage inflammatory protein-1alpha (MIP-1alpha) is an interesting chemokine because in addition to its variety proinflammatory activities including chemotaxis and immunomodulation, it is a potent inhibitor of hematopoetic stem cell proliferation. Inhibition of erythroid progenitor cells due to MIP-1alpha or other cytokines can play a role in the pathogenesis of anemia which is one of the most common extra-articular features of active rheumatoid arthritis (RA). In 84 patients with RA, serological and immunological parameters were assessed to detect inflammatory mechanisms and anemia in relation to the serum concentrations of MIP-1alpha. All patients fulfilled the ACR criteria for the diagnosis of a definite or classic RA. We used a quantitative enzyme immuno assay for the detection of MIP-1alpha as well as for the measurement of the acute phase protein serum amyloid A (SAA), the erythropoiesis inducer erythropoietin (EPO) and the transferrin receptor (TfR). The immune activation marker neopterin was measured radioimmunologically. Half of the patients with RA were anemic with hemoglobin values below 12 g/dl. MIP-1alpha was found to be elevated significantly in serum of patients with active rheumatoid arthritis and in patients with anemia. Most of the anemic patients with markedly elevated acute phase reactions had an anemia with chronic diseases and not a functional iron deficiency alone. TfR correlated with EPO. The results show that enhanced expression of MIP-1alpha is indicative of systemic inflammation in RA. Moreover, besides the regulation of inflammatory processes, this chemokine may influence the pathogenesis of anemia in RA patients.     

A CASE OF HEPATOCELLULAR ADKNOMATOSIS WITH A FOLLOW-UP OF 11 YEARS

Hepatoccllular adenomatosis is characterized by the presence of numerous (arbitrarily > 10) adenomas within an otherwise normal liver without a history of glycogen storage disease or steroid hormone therapy. Although the disease is rare, its importance lies in its tendency to produce symptoms such as abdominal pain and its potential for abdominal hemorrhages. However, the prognosis of hepatocellular adenomatosis remains uncertain. Here we describe the ease of a -40-yr-old female with hepatoccllular adenomatosis without evidence of serious complications, who was observed over a period of 11 yr.     

Molecular genetic characterization and urinary excretion pattern of metabolites in two families with MCAD deficiency due to compound heterozygosity with a 13 base pair insertion in one allele

Summary Two families with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency due to compound heterozygosity are described. All patients have a 13 bp insertion in exon 11 of one allele at the MCAD gene locus. In the other allele patients in one of the families harbour the prevalent G985 mutation, and the other family possess an unidentified mutation causing reduced levels of MCAD mRNA. We demonstrate that the disease in these families is inherited as an autosomal recessive trait. Individuals heterozygous for the mutations show heterozygous/control levels of -oxidation activities in cultured fibroblasts (9.1–16.3 pmol/min per mg protein; control 10–17 pmol/min per mg protein), and in the excretion of the -oxidation metabolites, hexanoylglycine (<2 µmol/mmol creatinine), suberylglycine (<2 µmol/mmol creatinine) and phenylpropionylglycine (<2 µmol/mmol creatinine). This shows that there is no negative dominance from the mutant monomeric protein onto the normal ones, in accordance with the finding of low levels of MCAD mRNA from the allele harbouring the 13 bp insertion as well as the allele with the unidentified mutation, and the low steady-state level of enzyme protein expressed from the G985-bearing allele. In the family possessing the G985 and the 13 bp insertion mutations, two asymptomatic compound heterozygous individuals were detected. They exhibited elevated excretion of hexanoylglycine (5–15 µmol/mmol creatinine) and suberylglycine (4–13 µmol/mmol creatinine), together with -oxidation activity in fibroblasts in the homozygous range (2.9 pmol/min per mg protein), showing a lack of correlation between the genotype, some biochemical parameters and the clinical phenotype.     

Excretion pattern of branched-chain amino acid metabolites during the course of acute infections in a patient with methylmalonic acidaemia

A 1-year-old boy with a typical B₁₂-responsive form of methylmalonic acidaemia was hospitalized twice due to acute bacterial infections. On both occasions, the child was lethargic with a severe ketoacidosis on admission. Intensive therapy with protein restriction, intravenous administration of electrolytes and antibiotics was effective within 4 days on both occasions. The urinary excretion of organic acids showed the same pattern on both occasions. There were rising excretion concentrations, reaching a peak value within the first 24-hour period, for the following compounds: 3-hydroxybutyric acid, 3-hydroxypropionic acid, 3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid. Excretion concentrations of the following rose for 48 h: isobutyric acid, 2-methylbutyric acid, isovaleric acid, lactic acid and the 2-oxo-acids. There was no increase until 12–24 h after the onset of severe illness in the excretion of propionic acid and methylmalonic acid. Propionic acid excretion was maximal at about 48 h, while peak excretion of methylmalonic acid was delayed until about 72 h after the onset of severe illness; at this time there was clinical improvement. The biochemical implications of this excretion pattern are discussed. This work has been supported by a grant from the Danish Medical Research Council.