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The purpose of this study was to measure the content of iron (Fe) in liver tissue samples from urbanized Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver tissue samples from urbanized Danes. Normal liver tissue samples were obtained at autopsy from 50 Greenlandic Inuit (27 men, 23 women) with a median age of 61 years (range 23-83) and from 72 Danes (42 men, 30 women) with a median age of 62 years (range 15-87). In the entire series, there was no significant difference between liver iron in Inuit compared with Danes. Likewise, there was no significant gender difference concerning liver iron content, either in Inuit or in Danes. The median iron content (with 5-95 percentile) in Inuit was 17.23 mmol/kg dry liver (5.80-91.80) and in Danes 16.51 mmol/kg dry liver (7.83-39.05). However, when stratified according to age, a trend was revealed showing that Inuit men and womenor = 50 years had a lower liver iron content than Danes (p = 0.05 and p = 0.08) whereas Inuit men and women50 years had a higher liver iron content than Danes (p = 0.18 and p = 0.02). There was a significant correlation between liver iron content and age in both Inuit men (rs = 0.49, p = 0.01) and in women (rs = 0.64, p = 0.003), but not in Danes. In Inuit, the median hepatic iron index (liver iron content divided by age) was 0.33 in men and 0.32 in women. The median estimated iron content in the whole liver was 6.54 mmol (365 mg) in Inuit men and 5.41 mmol (302 mg) in Inuit women (p = 0.6). There was no correlation between hepatic iron index and age. In Danes, the median hepatic iron index was 0.46 in men and 0.29 in women (p = 0.01). There was a significant inverse correlation between hepatic iron index and age in the two genders and in the entire series (rs = -0.71, p = 0.0001). The results indicate that young and middle-aged urbanized Inuit have slightly smaller iron stores than urbanized Danes, whereas elderly Inuit have higher iron stores than Danes. In Danes, iron stores plateau at 30 to 40 years of age in men and some years after the menopause in women. In Inuit, iron stores continue to increase in old age, probably to due a lifelong dietary intake of haem iron.

Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite. Here we report a transcriptome-based approach to identify novel pre-erythrocytic vaccine antigens that could potentially be used in combination with CSP. We hypothesized that stage-specific upregulated genes would enrich for protective vaccine targets, and used tiling microarray to identify P. falciparum genes transcribed at higher levels during liver stage versus sporozoite or blood stages of development. We prepared DNA vaccines for 21 genes using the predicted orthologues in P. yoelii and P. berghei and tested their efficacy using different delivery methods against pre-erythrocytic malaria in rodent models. In our primary screen using P. yoelii in BALB/c mice, we found that 16 antigens significantly reduced liver stage parasite burden. In our confirmatory screen using P. berghei in C57Bl/6 mice, we confirmed 6 antigens that were protective in both models. Two antigens, when combined with CSP, provided significantly greater protection than CSP alone in both models. Based on the observations reported here, transcriptional patterns of Plasmodium genes can be useful in identifying novel pre-erythrocytic antigens that induce protective immunity alone or in combination with CSP.

We evaluated the influence of Helicobacter pylori (H. pylori) infection assessed by the levels of H. pylori serum IgG-antibodies, on iron status (serum ferritin and haemoglobin) in 2794 Danes (1425 men), aged 30-60 years. The seroprevalence of H. pylori antibodies increased with age (p0.01). Median serum ferritin levels were significantly lower in seropositive than in seronegative men and postmenopausal women (men 114 micrograms/L vs. 120 micrograms/L, p = 0.01; premenopausal women 37 micrograms/L vs. 40 micrograms/L, p = 0.13; postmenopausal women 63 micrograms/L vs. 77 micrograms/L, p = 0.02). Seropositive subjects had a higher prevalence of iron deficiency (serum ferritin15 micrograms/L) than seronegative subjects. H. pylori infection has a negative influence on iron status. We hypothesize that this may be caused by increased blood losses from the gastric mucosa.

Chlamydia pneumoniae (C.pn.) is claimed to be of importance for the development of bronchial asthma in previously healthy individuals. This is a new and speculative theory. Earlier studies have mainly focused on C.pn. and exacerbation of asthma. If this new theory were true, one would expect titres of C.pn.-specific IgG to be higher or more common in patients compared with controls. It would also seem probable that pathobiological mechanisms as found in connection with other microorganisms could be demonstrated, i.e. presence of C.pn.-specific IgE and the capability of C.pn. to induce or enhance histamine release from basophil leukocytes. We therefore examined C.pn.-specific IgE, IgG and IgM in sera from 22 adults with bronchial asthma and 25 healthy controls. IgE was verified by passive sensitization of basophils from umbilical cord blood. The prevalence of IgE was approx. 69% and IgG approx. 23% in both groups. IgG-titres were between 1:16 and 1:64 in both groups. No IgM was found. Further, C.pn. could neither induce nor enhance histamine release from basophil leukocytes of patients or controls. We conclude that patients with bronchial asthma and healthy controls do not differ in relation to 1) C.pn.-specific IgE in sera, 2) the capability of C.pn. to induce or enhance histamine release from basophil leukocytes, since no such effect was found, or 3) previous C.pn. infection judged by the presence of specific IgG antibodies. Our results cannot support the theory that C.pn. is a cause of adult-onset asthma.

Iron status was assessed by measuring serum ferritin and haemoglobin in a population survey in Copenhagen County, comprising 1359 nonpregnant women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Premenopausal women had lower serum ferritin (median 37 micrograms/l) than postmenopausal women (median 71 micrograms/l), p0.0001. Of premenopausal women, 17.7% had ferritin15 micrograms/l (depleted iron stores), and 23.1% had ferritin levels of 15-30 micrograms/l (small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Iron deficiency anaemia (ferritin15 micrograms/l and haemoglobin121 g/l) was observed in 2.6% of pre- and 0.36% of postmenopausal women. After menstruations had ceased, there was a steep rise in ferritin levels, being most pronounced during the first 7 postmenopausal years. Pre- and postmenopausal multipara had lower ferritin than nulli- and unipara (p0.04), indicating that pregnancy and childbirth had a long lasting reducing influence on iron stores. The use of oral hormonal contraceptives had a marked increasing effect on iron stores, being correlated to the number of years the women had been taking the pill.

Bone marrow haemosiderin iron grade and serum (S-) iron status markers (haemoglobin (Hb), S-iron, S-transferrin, transferrin saturation, S-ferritin) were measured in 31 patients with newly discovered small cell cancer of the lung (SCCL), and compared to the values in 53 healthy control subjects. Among SCCL patients, 2 had grade 0 (absent), 5 grade (1+) (trace), 8 grade 1+ (normal), and 16 grade 2+ (increased) marrow haemosiderin iron. Median S-ferritin values in the respective groups were 38 mug/l, 243 mug/l, 384 mug/l and 433 mug/l. There was no correlation between Hb, S-iron, S-transferrin or transferrin saturation and marrow iron grade. S-ferritin displayed a correlation with marrow iron grade (r(s) = 0.40, p

The major extracellular enzyme of Legionella pneumophila, a metalloprotease, has been proposed as a pathogenic factor in Legionnaires' disease due to its cytotoxic, tissue-destructive, and phagocyte-inhibitory properties. The relevance of these activities depends on the production of the protease during infection, i.e. by L. pneumophila multiplying intracellularly. In this study, L. pneumophila was demonstrated to produce protease in guinea-pig and human alveolar macrophages infected in vitro. After 24 h infection, approximately 0.1 to 0.2 micrograms of protease per 10(6) bacteria was measured by ELISA in culture supernatants and lysates of the infected cells, whereas no protease could be detected immediately after infection. Immunogold labelling using anti-protease antibody showed the enzyme to be located within phagosomes and distributed throughout the macrophages. Recent observations have shown that this protease could modify host defence mechanisms through inhibition of bacterial killing by neutrophils and monocytes. The intracellular production of the enzyme in infected macrophages demonstrated here further supports a role for the protease in the pathogenesis of Legionnaires' disease.

Iron stores were evaluated by serum ferritin determinations in 948 menstruating and 141 non-menstruating female blood donors. Blood donation was associated with a decrease in ferritin. First-time donors (n = 163) had a geometric mean ferritin of 24 micrograms/l and multiple-time donors a value of 19 micrograms/l (p less than 0.01). In the donating population 31.5% had ferritin values less than 15 micrograms/l (i.e. depleted iron stores). Menstruating donors had lower mean serum ferritin than non-menstruating donors (p less than 0.001), and a higher frequency of ferritin values less than 15 micrograms/l (p less than 0.05). There was no relationship between ferritin levels and the number of pregnancies. The frequency of donations was more predictive of ferritin levels than the number of donations. Mean ferritin displayed a moderate fall up to the 2nd donation, and was hereafter relatively constant, whereas an increase in donation frequency was accompanied by a significant decrease in ferritin. Female donors, especially when phlebotomised greater than or equal to 3 times per year, should have their iron status checked at appropriate intervals by measurement of serum ferritin and should be advised regular iron supplementation.

The synovial fluid ferritin level in 49 patients (57 joints) with various rheumatic diseases was analysed. In rheumatoid arthritis (n = 22) the geometric mean ferritin level was 528 micrograms/l (range 56-3 100 micrograms/l), in other inflammatory arthritides (n = 12) 339 micrograms/l (105-2 835 micrograms/l) (p greater than 0.5), in calcium pyrophosphate arthropathy (n = 14) 507 micrograms/l (180-4 230 micrograms/l) (p greater than 0.5) and in non-inflammatory osteoarthritis (n = 9) 167 micrograms/l (14-725 micrograms/l) (p less than 0.05). Synovial fluid/serum ferritin ratios did not differ significantly in the four diagnostic groups; 4 patients had ratios less than 1.0. Synovial fluid ferritin was not correlated to total fluid cell count or differential cell count. Although ferritin content was significantly greater in inflammatory than in noninflammatory fluid (p less than 0.05), the wide scatter of the values and marked overlap between the different groups limit the value of measuring synovial fluid ferritin as a differential diagnostic test for rheumatic diseases.

Serum ferritin and biochemical liver tests (serum bilirubin, serum aspartate transaminase, serum gamma-glutamyl transpeptidase (gamma-GT), and serum alkaline phosphatase) were recorded at regular intervals from admission to recovery in six patients with acute viral hepatitis. There was a proportional, significant decrease in ferritin bilirubin, and transaminase were reached simultaneously, whereas gamma-GT and alkaline phosphatase remained elevated for a slightly longer time. The correlations between corresponding measurements of ferritin and biochemical liver tests were as follows: ferritin and alkaline phosphatase, r = 0.72, P less than 0.001; ferritin and bilirubin, r = 0.68, P less than 0.001; ferritin and transaminase, r = 0.53, P less than 0.001; ferritin and gamma-GT. r = 0.50, P less than 0.001. In viral hepatitis serum ferritin offers no diagnostic advantage compared with already established tests for hepatocellular damage.

To investigate the association of individual plots and time-integrated values of repeated measures of inflammatory variables with radiographic outcome in rheumatoid arthritis (RA).In 112 patients with RA, examinations of joint swelling and joint tenderness of 68 joints, and measurement of hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) were performed each year for up to 22 years after the first visit. For each of these 4 variables, the patients were divided arbitrarily into 5 characteristic subgroups by means of inspection of individual plots of longitudinal observations of the variables and divided into 5 other subgroups according to 20% percentiles of the cumulative mean values of the variables. The outcome of the subgroups was evaluated by varying degrees of radiographic events estimated by Larsen scoring of consecutive radiographs of 46 joints.An increasing number of radiographic events in subgroups with increasing severity (increasing values of joint swelling, joint tenderness, and ESR, decreasing values of Hb) was seen for both the arbitrary subgroups and the percentile subgroups of joint swelling, Hb, and ESR, whereas the association of joint tenderness to radiographic progression was weak.A highly significant association between inflammatory variables and radiographic outcome could be observed, indicating that the degree of inflammation is important for the development of destructive joint damage in RA.

Among fertile, nonpregnant, Danish women, 33% have absent or reduced iron stores; 22% have serum ferritin values above 70 micrograms/l, i.e., iron reserves of more than 530 mg, corresponding to the net iron losses during a normal pregnancy. During pregnancy, the demands for absorbed iron increase from 0.8 to 7.5 mg/day. Controlled studies show that iron-treated pregnant women have higher serum ferritin levels, i.e., larger iron stores, and higher haemoglobin levels than placebo-treated women. A supplement of 66 mg ferrous iron daily from the beginning of the 2nd trimester prevents iron deficiency anaemia. In Denmark, general iron prophylaxis with 60-70 mg ferrous iron daily from 20 weeks of gestation is recommended by the health authorities.

Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae) and Branhamella catarrhalis (B. catarrhalis) are often found in the lower respiratory tract of patients with chronic bronchitis. Earlier studies have shown that bacteria induce mediator release from human basophils and parenchymal lung mast cells. In this study the capability of bacteria to trigger or potentiate histamine release from superficially located mast cells in the airway epithelium was studied in cell suspensions obtained by bronchoalveolar lavage in patients with chronic bronchitis (CB). In approximately half of the patients H. influenzae and Staphylococcus aureus (S. aureus) were found to trigger histamine release, whereas no response was obtained by S. pneumoniae or B. catarrhalis. The mediator release was caused by a non-IgE-dependent mechanism. At lower concentrations of H. influenzae causing no histamine release the bacterium was found to enhance IgE-mediated histamine release triggered by anti-IgE antibody. The synergy was more pronounced in patients with CB than in controls. Since H. influenzae is found in the lower respiratory tract of the patients but not in normal individuals, the infection here may via histamine release lead to harmful effects on the airways of importance for precipitation and exacerbation of chronic bronchitis.