The binding of quinidine to protein fractions of normal human sera.

In contrast to previous assumptions, albumin is not the only protein in normal human serum responsible for binding quinidine. Human serum proteins were fractionated by gel filtration and floatation. Quinidine binding was determined by equilibrium dialysis. The binding to low (LDL) and high (HDL) density lipoproteins exhibited two binding sites on each protein, and the dissociation constants K and number of binding sites n were calculated. LDL: K₁ = 2 × 10^?5, n₁ = 1 and K₂ = 5·2 × 10^?4, n₂ = 97. HDL: K₁ = 1·9 × 10^?5, n₁ = 0·1 and K₂ = 1·1 × 10^?3, n₂ = 14·7.     

Subcellular localization of transferrin and pyrophosphate in liver cells after perfusion in situ or incubation in vitro.

Rat livers were perfused in situ with [125I]-transferrin, FITC-dextran and [32P]-inorganic pyrophosphate (PP). In a parallel set of experiments rat liver homogenates was incubated with [125I]-transferrin and [32P]-PPi. In both sets of experiments cellular organelles were prepared by density gradient centrifugation in metrizamide. In the perfusion experiments [125I]-transferrin and FITC-dextran accumulated in fractions rich in plasma membrane enzymes, whereas in the homogenate experiments [125I]-transferrin remained in soluble fractions. [32P]-PPi remained in soluble fractions in both sets of experiments, i.e. PPi did not co-localize with transferrin taken up by intact cells. In another set of experiments fractions rich in endosomes were tested for their ability to synthesize PPi from ATP. No PPi was found. The results argue against a role for PPi in transferrin-iron release within endosomes.     

Alveolar macrophages from expectorates as indicators of pulmonary irritation in primary aluminum reduction plant workers

According to a method (the AM-test) previously developed by us, the counting of alveolar macrophages (AM) from expectorates provides an estimation of the potential pulmonary insult from occupational air pollution +/- smoking. In this article we demonstrate a relationship between the number of AM and self-registered pulmonary symptoms and complaints. Employees from different workplaces in a primary aluminum reduction plant gave expectorate samples for the AM-test. A gradient in the number of AM was observed, with increasing AM numbers from the controls to the administration employees to the potroom workers, who had the highest numbers. Pulmonary symptoms and complaints were recorded by means of a questionnaire. A clear covariation between AM numbers and respiratory symptoms and complaints was observed and was most pronounced at the highest pollution levels (in the potrooms). We therefore suggest that the AM-test may serve as an effect indicator as well as a dose indicator.     

Folate supplementation and twin pregnancies

BACKGROUND: Women in many countries are advised to increase their folate intake to lower the risk of neural tube defects. For this purpose several countries add folate to the flour. Therefore, it is important to monitor possible adverse effects of this B vitamin. We have assessed the effect of folate on twin pregnancies. METHODS: We conducted a retrospective, population-register based study of 176,042 women who gave birth from December 1998 through the end of 2001. Use of folate and multivitamin supplements was recorded on the mandatory birth notification form of the Medical Birth Registry of Norway. Pregnancies after in vitro fertilization (IVF) were reported separately. RESULTS: With adjustment for maternal age and parity, we observed an increased risk of twin pregnancies associated with preconceptional use of folate (odds ratio = 1.59; 95% confidence interval = 1.41-1.78). This association was largely explained by confounding with IVF pregnancies, which were strongly associated both with twin pregnancies and folate use. After exclusion of known IVF pregnancies, and accounting for underreporting of both IVF pregnancies and folate use, the risk was no longer elevated (1.02; 0.85-1.24). Weak associations with twin pregnancies were observed for use of multivitamins and folate during pregnancy, but could be due to increased use of vitamins after a recognized twin pregnancy. CONCLUSIONS: The association between preconceptional folate use and twin pregnancies was strongly confounded by IVF. After accounting for IVF pregnancies and underreporting, we found no evidence for an association between preconceptional folate supplements and twinning.     

Increased expression of fas ligand in human tuberculosis and leprosy lesions: a potential novel mechanism of immune evasion in mycobacterial infection

To study the location and mechanism of apoptosis within the human tuberculosis (TB) and leprosy lesions, parallel sections were analyzed for mycobacterial antigens (M.Ag), Fas ligand (FasL), Fas, CD68 and Mac387 by immunohistochemistry, and apoptotic cells by the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling method. Cutaneous leishmaniasis and foreign body granulomas were analyzed for comparison. The heavily infected macrophages in multibacillary TB and leprosy granulomas very strongly expressed FasL, indicating that a mycobacterial infection can induce an increased expression of FasL in a population of infected macrophages, which may protect them from the attack of Fas-expressing lymphocytes. However, macrophages with high levels of leishmania amastigotes did not selectively express FasL, suggesting that this phenomenon is specific for the mycobacteria. Interestingly, in the well-formed TB granulomas, 84% of the multinucleated giant cells strongly expressed FasL. The expression of Fas was weak (34%) or absent. A higher number (33%) of epithelioid cells expressed FasL than Fas (23%). Lymphocytes were scanty among the epithelioid cells. The frequency of apoptotic cells was higher in the epithelioid cells (0.25%) than the mononuclear cells in the mantle zone (0.14%). Thus, the epithelioid cells and the multinucleated giant cells by virtue of the increased expression of FasL may make these granulomas an immune privileged site for mycobacteria.