Detection of polyomavirus BK and JC in children with kidney diseases and renal transplant recipients

BACKGROUND: Reactivation of polyomavirus is a known reason for severe renal dysfunction in adult renal transplant recipients. Testing for polyomavirus DNA in plasma has been described as a sensitive and specific method to discover viral nephropathy in adult patients. We were now interested in polyomavirus status in a pediatric patient setting. METHODS: Plasma and urine samples were obtained from 80 children including 38 children after renal transplantation (group 1), 7 children with different kidney diseases receiving immunosuppressive treatment (group 2) and 35 children with different kidney diseases not receiving immunosuppressive treatment (group 3). A nested polymerase chain reaction method was used for amplification of polyomavirus DNA fragments. Differentiation between JC and BK virus was done by digestion with restriction endonucleases. RESULTS: Polyomavirus DNA was detected in the urine sample of 19 of 38 (50%) renal transplant recipients (group 1), of 1 of 7 (14%) patients from group 2 and in none of the 35 patients of group 3. Plasma samples from 3 (8%) of group 1 patients and from 1 child each of group 2 (14%) and group 3 (3%) were tested positive for polyomavirus DNA. CONCLUSION: Urinary polyomavirus excretion seems to be more frequent in pediatric patients with kidney diseases receiving immunosuppressive treatment and after renal transplantation than in children with various kidney diseases without immunosuppressive treatment.     

Current Therapy of Pulmonary Hypertension

Abstract Pulmonary arterial hypertension (PAH) affects vascular proliferation and remodeling in small pulmonary arteries and results in right ventricular failure and death due to a progressive increase in pulmonary vascular resistance. Recent advances in understanding of the molecular mechanisms involved in PAH suggest that endothelial dysfunction plays a major role. Impaired production of vasoactive mediators, such as prostacyclin and nitric oxide, accompanied with prolonged overexpression of vasoconstrictors such as endothelin-1, affects vascular tone and reinforces vascular remodeling. As the latter substances represent logical pharmacological targets, new drugs affecting these mechanisms have evolved during the past 2 decades and led to umpteen placebo-controlled trials in bygone years. Prognosis and quality of life of patients suffering from PAH seem to improve due to these new treatment strategies resulting in a reduction of mortality and morbidity, but there is still a substantial need for further long-term and head-to-head trials.     

A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior

Sex differences in brain and behavior are ubiquitous in sexually reproducing species. One cause of sexual dimorphisms is developmental differences in circulating concentrations of gonadal steroids. Neonatal testes produce androgens; thus, males are exposed to both testosterone and estradiol, whereas females are not exposed to high concentrations of either hormone until puberty. Classically, the development of neural sex differences is initiated by estradiol, which activates two processes in male neonates; masculinization, the development of male-type behaviors, and defeminization, the loss of the ability to display female-type behaviors. Here, we test the hypothesis that defeminization is regulated by estrogen receptor beta (ERbeta). Adult male ERbeta knockout and WT mice were gonadectomized, treated with female priming hormones, and tested for receptive behavior. Indicative of incomplete defeminization, male ERbeta knockout mice showed significantly higher levels of female receptivity as compared with WT littermates. Testes-intact males did not differ in any aspects of their male sexual behavior, regardless of genotype. In olfactory preference tests, males of both genotypes showed equivalent preferences for female-soiled bedding. Based on these results, we hypothesize that ERbeta is involved in defeminization of brain and behavior. This aspect of ERbeta function may lead to developments in our understanding of neural-based sexually dimorphic human behaviors.     

Expression and regulation of<Emphasis Type="Italic"> ROR-1</Emphasis> during early avian limb development

ROR-1 is a member of the ROR family of tyrosine kinase like orphan receptors and is highly conserved among various species. We have isolated the chickROR-1 (cROR-1) and show that cROR-1 expression is high and restricted to the proximal limb region until HH-stage 25. At later stages, expression spreads towards the distal limb region. In order to determine the signals that control cROR-1 expression, factors known to be involved in limb patterning (FGFs, BMPs, SHH, retinoic acid) were applied to the developing limb. Whereas neither FGFs, BMPs, nor SHH affected cROR-1 expression, upregulation could be achieved by ectopic application of retinoic acid to the distal limb region. As retinoic acid also upregulated retinoic acid receptor beta (Rar-β), we assume that cROR-1 upregulation is mediated by Rar-β. We conclude that ROR-1 signaling is an independently regulated pathway, which is involved in late rather than early limb development.     

Expression and regulation of ROR-1 during early avian limb development

ROR-1 is a member of the ROR family of tyrosine kinase like orphan receptors and is highly conserved among various species. We have isolated the chick ROR-1 (cROR-1) and show that cROR-1 expression is high and restricted to the proximal limb region until HH-stage 25. At later stages, expression spreads towards the distal limb region. In order to determine the signals that control cROR-1 expression, factors known to be involved in limb patterning (FGFs, BMPs, SHH, retinoic acid) were applied to the developing limb. Whereas neither FGFs, BMPs, nor SHH affected cROR-1 expression, upregulation could be achieved by ectopic application of retinoic acid to the distal limb region. As retinoic acid also upregulated retinoic acid receptor beta (Rar-), we assume that cROR-1 upregulation is mediated by Rar-. We conclude that ROR-1 signaling is an independently regulated pathway, which is involved in late rather than early limb development.     

Formation and differentiation of the avian dermomyotome

During somite maturation, the ventral half of the epithelial somite disintegrates into the mesenchymal sclerotome, whereas the dorsal half forms a transitory epithelial sheet, the dermomyotome, lying in between the sclerotome and the surface ectoderm. The dermomyotome is the source of most of the mesodermal tissues in the body, giving rise to cell types as different as muscle, connective tissue, endothelium, and cartilage. Thus, the dermomyotome is the most important turntable of mesodermal cell fate choice in the vertebrate embryo. Here, we discuss the current knowledge on the formation of the dermomyotome and the mechanisms leading to the development of the various dermomyotomal derivatives, with special emphasis on the development of musculature and dermis.     

Coronary flow reserve measurements in hypertension

Taken together, the diagnostic algorithm is leaded by a simple ECG stress test. In case of ST-segment depression the preferred image test should be stress ECG to bring patients at high risk for significant epicardial coronary artery stenosis to coronary angiography (and revascularization). In case of the lack of wall motion abnormalities (during stress-echo test) or absence of epicardial stenosis one may further assess coronary flow reserve with noninvasive Doppler harmonic echocardiography. For ultimate quantitative assessment invasive procedures, such as argon dilution or intracoronary Doppler techniques, represent the appropriate approach. Treatment of microvascular disease may be followed-up by these new noninvasive diagnostic approaches in future and also, at present, by monitoring ST-segment depression.