IDR: the ImmunoDeficiency Resource

The ImmunoDeficiency Resource (IDR), freely available at http://www.uta.fi/imt/bioinfo/idr/, is a comprehensive knowledge base on immunodeficiencies. It is designed for different user groups such as researchers, physicians and nurses as well as patients and their families and the general public. Information on immunodeficiencies is stored as fact files, which are disease- and gene-based information resources. We have developed an inherited disease markup language (IDML) data model, which is designed for storing disease- and gene-specific data in extensible markup language (XML) format. The fact files written by the IDML can be used to present data in different contexts and platforms. All the information in the IDR is validated by expert curators.     

Loss of habitats,naturalness and species diversity in Eurasian forest landscapes

Man has exploited land and forests in Western and Central Europe longer and more intensively than in Northern Europe and further east in Eurasia. We estimated forest naturalness and modelled expected biodiversity loss in seven different landscapes (2500 km² each) in the Netherlands, Sweden, Finland, Poland, St. Petersburg (Western European Russia), Perm (Eastern European Russia), and Irkutsk (Central Siberia) across the distribution of Pinus sylvestris L. in Eurasia. Field inventories showed that the mean living tree volumes were relatively similar in the studied sites, but the volumes of dead wood differed greatly. In Irkutsk and Perm the volume of dead trees per ha was about 5–10 times larger than in Central and Western European regions. The studied forests were generally young in all regions except for Irkutsk, where about half of the study plots had trees older than 120 years. Signs of recent forest fires were found almost exclusively on Russian sites. According to Landsat satellite image-based land-cover classifications the amount of remaining forest habitat in the studied landscapes varied from 25% in the Netherlands to 93% in Irkutsk. Estimated by forest patch size and density of cut stumps, forests were also more fragmented and heavily managed in the western study landscapes compared to eastern ones. Based on species–area relationship functions, we calculated that the proportion of forest-dwelling species already extinct or expected to become extinct due to habitat loss ranges from 1–2% in Irkutsk to 13–24% in the Netherlands study landscape. For saproxylic species, which depend on dead wood, the extinction estimates were calculated based on remaining dead wood volume in the landscape. The modelled expected loss of saproxylic species ranged from 7–14% in Irkutsk to 35–58% in the Netherlands.     

Extraction and purification of DNA in rhizosphere soil samples for PCR-DGGE analysis of bacterial consortia

Application of DNA fingerprinting methods enables the detection of diverse members of soil bacterial consortia, even including those bacteria not yet cultivated. However, extraction and purification of DNA from soil samples without bias is difficult. We compared five different DNA isolation methods and three purification methods for rhizosphere soil samples. Purified DNA extracts were amplified in PCR using universal bacterial primers and the PCR products were analysed with denaturing gradient gel electrophoresis (DGGE) for the visualisation of DNA bands representing dominant bacterial species. Both the isolation and purification methods affected the apparent bacterial community structure of the samples.     

Human natural cell-mediated cytotoxicity against fetal fibroblasts. III. Morphological and functional characterization of the effector cells

We have isolated and characterized human natural killer cells cytotoxic to human fetal fibroblasts utilizing adsorption-elution of the effector cells from target cell-coated beads. The cell associated with enriched cytotoxicity was slightly larger than small- to medium-sized lymphocytes, the cytoplasm was pale and characteristically granular. In direct surface marker analysis the cell was Fc-receptor-positive, formed E-rosettes, and displayed strong either diffuse or granular ANAE reactivity in the cytoplasm. The ANAE reactivity could not be inhibited with sodium fluoride and in mitogen and antigen stimulation experiments the cell had T-cell characteristicis. The cell type was termed large granular lymphocyte and we suggest that it is the main direct effector cell for natural killer activity against human fetal fibroblasts.     

Prognostic value of non-MHC-restricted killer cell activity in lung cancer

The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II–IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II–IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyound that already available from staging. However, those stage II–IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.     

Common genetic and environmental effects on lipid phenotypes: the HERITAGE family study

OBJECTIVE: Despite the well known genetic component influencing plasma lipid-lipoprotein levels and the observed correlations among these traits, little is known about pleiotropic heritable determinants among them. Our aim is to investigate pair-wise polygenic and environmental correlations among lipid-lipoprotein levels at baseline and in response to regular exercise in Whites and Blacks. METHODS: Common pair-wise genetic and environmental correlations among levels of total cholesterol (TC), LDL-C, ApoB, HDL-C (also HDL2-C and HDL3-C), triglycerides (TG, HDL-TG and LDL-TG) and ApoA-1 were investigated at baseline and again after a 20-week endurance exercise program using a variance-components-decomposition. RESULTS: With a few exceptions, all lipid phenotypes were heritable at baseline and for training responses in Blacks and Whites. Strong to high genetic and environmental correlations (0.4 < rho(g) < 0.7) were observed for the majority of the baseline pair-wise traits. For training responses, many of the same patterns were noted, although fewer genetic correlations were significant as compared to the baseline results. CONCLUSIONS: Results suggest that the observed phenotypic correlations among many of these traits may be due to in part to pleiotropic genes, in particular between LDL-C and ApoB and between TG and HDL-C. This shared genetic architecture should be considered in follow-up gene finding studies.