TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals.

The urinary excretion of retinol-binding protein (RBP), beta 2-microglobulin (beta 2-m), and beta-N-acetyl-D-glucosaminidase was monitored in patients with renal tubular damage secondary to multiple injuries, rhabdomyolysis, antibiotic treatment, or poisoning by various chemicals such as solvents, heavy metals, or pesticides. In almost all cases, RBP proved to be a more sensitive index of renal tubular damage than was beta-N-acetyl-D-glucosaminidase and, being more stable in acid urine, a more practical analyte to measure than was beta 2-m. We corroborated this finding by studying the relationships between these three analytes in more than 150 patients. On the average, an increase in the urinary excretion of beta-N-acetyl-D-glucosaminidase becomes detectable when urinary RBP already exceeds the normal value by 50- to 100-fold. In urines with pH greater than 6, RBP and beta 2-m concentrations are well correlated (r = 0.93, n = 150), beta 2-m tending to be more frequently positive (i.e., greater than 311 micrograms/L). But in urines with pH less than 6 (about 30-40% of the samples), the RBP/beta 2-m concentration ratio increases as pH decreases, up to 500 in some patients with massive tubular injury. Because the renal uptake of proteins involves a saturable process, the urinary excretion of RBP, like that of beta 2-m, specifically reflects the reabsorption capacity of proximal tubules only when the glomerular filtration rate is normal or slightly impaired (i.e., serum creatinine less than 20 mg/L). Under these conditions the determination of RBP protein in urine appears the most appropriate test when early detection of tubular injury is desirable.

We investigated possible immunological changes in 15 professional football players before, during and after the sports season. We studied the leucocyte count as well as different functions such as T-lymphocyte proliferation, NK activity, chemotaxis and phagocytosis of neutrophils. Training and competitions did not produce any change in the total number of leucocytes but increased neutrophil counts and decreased T4 lymphocyte counts. We also observed a slight decrease of T-lymphocyte proliferation and a significant decrease of neutrophil functions. On the other hand, training and competitions did not induce significant changes in the number of NK cells nor in the total NK cytotoxic activity. The different change observed tended to normalize after the sports season. Our results suggest a predominant neutrophil function depression in football players during a training season which could partly explain the susceptibility of elite athletes to infections.

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Intestinal permeability was investigated in 10 normal young adults, in 11 control children and in 9 children presenting with either Berger disease (4 cases) or Henoch-Schönlein nephritis (5 cases), making use of (51 Cr) EDTA as a probe molecule. All subjects exhibited a normal creatinine clearance at the time of testing. After oral administration of (51 Cr) EDTA, 24-hour urine radioactivity was measured and results were expressed in percentage of the oral dose administered. Means and SD were 2.35% +/- 0.77, 2.51% +/- 0.70, and 5.10% +/- 2.35 for normal adults, control children and patients with IgA-associated nephropathies, respectively. The differences of permeability between controls and patients were statistically significant (p less than 0.01). In addition, a significant, direct, linear correlation has been established between the percentage of (51 Cr) EDTA excreted in 24-hour urine and IgA immune complex-plasma levels. Our results therefore support the hypothesis that increased gut permeability could play a role in the pathogenesis of IgA-associated nephropathies.