Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation.

BACKGROUND: The cytokine interleukin-4 (IL-4) is secreted mainly by activated T lymphocytes and characterizes the T-helper 2 (Th2) sub-type. In transplantation Th2 cells are believed to induce graft tolerance. Previous studies revealed that patients with a relatively high frequency of IL-4 producing helper T lymphocytes (HTL) before heart transplantation (HTX) had no or less rejection episodes compared with patients with a low frequency of IL-4 producing HTL. Three single nucleotide polymorphisms (SNPs) have been identified in the promoter region of the IL-4 gene, which influence promoter strength. We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection after HTX. METHODS: Seventy HTX patients, 61 donors, and 36 controls were genotyped for the 3 SNPs by sequencing. RESULTS: Of the SNPs at -285 and -81, only the C and A alleles, respectively, were found in this study. Both alleles were found for the -590 SNP. No relation between patient genotype of the SNP at -590 and heart failure and rejection was found. However, incidence of rejection was significantly lower in patients that received a donor heart with the T-positive genotype compared with patients that received a heart from a T-negative donor. Patients who had the T-negative genotype and received a heart from a T-positive donor, suffered significantly less from rejection than T-negative patients that received a T-negative donor heart. This was not significant in the T-positive patient group. CONCLUSIONS: This indicates that IL-4 production within the donor heart and by cells from the donor is important for reducing incidence of episodes of rejection.     

Treatment planning in residential institutions

In child and youth care in the Netherlands, systematic planning of treatment is more and more considered to be a condition for effective and well founded treatment. Although workers are convinced of the benefits of treatment plans, treatment planning is not yet a natural and integrated part of residential care. There are several pressure points. In this article a model of treatment planning will be presented that contributes to an answer to these pressure points. The theoretical bases and the practical implications of this model will be discussed.     

An analysis of fluid loss during transcervical resection of submucous myomas

Objective: To determine the contribution of several variables to fluid loss during transcervical resection of submucous myomas.Design: An observational study using multiple linear regression analyses.Setting: A university-affiliated training hospital and a university department of clinical epidemiology and biostatistics.Patient(s): Patients with submucous myomas.Intervention(s): Transcervical resection of submucous myomas and monitoring of fluid loss.Main Outcome Measure(s): Patient age, uterine enlargement, treatment with GnRH analogues or 8-ornithine-vasopressin, type of anesthesia, number of myomas, intramural extension of the myoma (type of myoma), and operating time were tested as variables.Result(s): Only intramural extension of the myoma and operating time were obviously related to fluid loss. For the other variables, such a relation was weak at best. The relation between fluid loss and operating time was not modified by any of the other variables.Conclusion(s): Because fluid loss is an important limiting factor in the transcervical resection of submucous myomas, special attention should be paid to reduction of the operating time and preoperative assessment of the intramural extension of the myoma to guide appropriate patient selection.     

Similarities in Skeletal Muscle Strength and Exercise Capacity Between Renal Transplant and Hemodialysis Patients

Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients. Aim of the study was to assess to what extent exercise capacity and skeletal muscle strength of RTx patients differ from HD patients and healthy controls and to elucidate potential determinants of exercise capacity in RTx patients. Exercise capacity, muscle strength, lean body mass (LBM) and physical activity level (PAL) were measured by cycle-ergometry, isokinetic dynamometry, DEXA and Baecke Questionnaire, respectively, in 35 RTx, 16 HD and 21 controls. VO2peak and muscle strength of the RTx patients were significantly lower compared to controls (p<0.01), but not different compared to HD patients. In RTx patients, strength (p<0.001), PAL (p=0.001) and age (p=0.045) were significant predictors of VO2peak. Muscle strength was related to LBM (p=0.001) and age (p=0.001), whereas gender (p<0.001) and renal function (p=0.01) turned out to be significant predictors of LBM. No effects of corticosteroids were observed. Exercise capacity and muscle strength seem equally reduced in RTx and HD patients compared to controls. In RTx patients, muscle strength and PAL are highly related to exercise capacity. Renal function appears to be a significant predictor of LBM, and through the LBM, of muscle strength and exercise capacity.     

Adenoviral vectors expressing siRNAs for discovery and validation of gene function

RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required. Here, we describe the validation of adenoviral vectors that express hairpin RNAs that are further processed to siRNAs. Infection of cell lines, or primary human cells, with these viruses leads to an efficient, sequence-specific, and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell. For knock-down of one of the targets, GalphaS, we have measured inhibition of ligand-dependent, G-protein-coupled signaling. It is expected that this technology will prove to be of great value in target validation and target discovery efforts.     

Responses against complex antigens in various models of CD4 T-cell deficiency

The most common models of CD4 T-cell deficiency are mice exogenously injected with anti-CD4 antibody (Ab), CD4 knockout (CD4^−/−) and major histocompatibility complex (MHC) class II knockout (class II^−/−) mice. We recently described the anti-CD4 Ab transgenic mouse (GK) as an improved CD4 cell-deficient model. This review compares this new GK mouse model with the widely available class II^−/− and CD4^−/− mice, when exposed to complex antigens (foreign grafts and during bacterial or viral infection). We highlight here the cytometric and functional differences (including Ab isotype, viral or bacterial clearance, and graft survival) among these CD4 cell-deficient models. For example, whereas grafts are generally rejected in class II^−/− and CD4^−/− mice as quickly as in wild-type mice, they survive longer in GK mice. Also, CD4^−/− mice produce IgG against both simple model and complex antigens, but class II^−/− and GK mice produce small amounts of IgG2a against complex antigens but not simple model antigens. These differences harbinger the caveats in the use of these various mice.     

SpecialEscherichia coli serotypes among enterotoxigenic strains from diarrhoea in adults and children

106 enterotoxigenicEscherichia coli strains from children and adults from many parts of the world were serotyped for O and H antigens. Some OH types,i.e. O6H16, O8H9, O15H11, O25H42, O78H11 and O78H12, were found repeatedly from different geographical locations. Some of these OH serotypes were only found rarely among more than 20000E. coli strains collected over many years from different locations and sources. It is suggested that these special OH serotypes represent clones which have been selected to the special conditions in the small intestine and selected to carry the plasmids necessary to provoke diarrhoea.