Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps

BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.     

Does a torn anterior cruciate ligament lead to change in the central nervous drive of the knee extensors?

Summary Integrated surface electromyograms of the three superficial parts of the quadriceps and isokinetic knee extensor maximum torque and power production were recorded simultaneously and at different angular velocities in both legs in 11 male subjects with unilateral tear of the anterior cruciate ligament. The cross-sectional area (CSA) of the thigh and its muscular components were measured by computerized tomography. The principal findings were a small but significant decrease in quadriceps CSA on the affected side; a decreased active, but not passive, range of movement; decreased mechanical output, whether or not corrected for differences in CSA; and decreased electrornyographic activity — particularly in rectus femoris. These findings suggest that the reason for the decreased maximum and total knee extensor performance seen in these patients is a change in knee joint receptor afferent inflow.     

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m2/g) were compared with beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2x10(5) expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 416 MSC/CDHA composites compared to 216 MSC/beta-TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls (p<0.001). Furthermore, ALP was significantly (p<0.05) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to beta-TCP blocks.     

Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection

Human immunodeficiency virus (HIV) has been isolated from plasma in 6 of 7 patients showing clinical symptoms of a primary HIV infection. Parallel cultures from peripheral blood mononuclear cells (PBMC) yielded virus in 5 patients. In one case, virus could only be isolated from the cerebrospinal fluid but not from peripheral blood. Detectable viremia was transient and preceded the appearance of HIV specific antibodies. After cessation of acute symptoms, the frequency of HIV isolations was similar to that of asymptomatic carriers (23 and 26%, respectively). The role of the immune response in terminating detectable viremia remains to be established.     

Treatments of pelvic girdle pain in pregnant women: adverse effects of standard treatment,acupuncture and stabilising exercises on the pregnancy,mother, delivery and the fetus/neonate

Background  

Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to standard treatment or standard treatment alone.     

Absolute pitch and pupillary response: effects of timbre and key color

The pitch identification performance of absolute pitch possessors has previously been shown to depend on pitch range, key color, and timbre of presented tones. In the present study, the dependence of pitch identification performance on key color and timbre of musical tones was examined by analyzing hit rates, reaction times, and pupillary responses of absolute pitch possessors (n = 9) and nonpossessors (n = 12) during a pitch identification task. Results revealed a significant dependence of pitch identification hit rate but not reaction time on timbre and key color in both groups. Among absolute pitch possessors, peak dilation of the pupil was significantly dependent on key color whereas the effect of timbre was marginally significant. Peak dilation of the pupil differed significantly between absolute pitch possessors and nonpossessors. The observed effects point to the importance of learning factors in the acquisition of absolute pitch.     

Optimisation of the CT h4S bioassay for detection of human interleukin-4 secreted by mononuclear cells stimulated by phytohaemaglutinin or by human leukocyte antigen mismatched mixed lymphocyte culture

Limiting dilution analysis has been used in the context of allogeneic bone marrow transplantation to determine anti-recipient interleukin-2 (IL-2) producing helper T lymphocyte precursor (HTLp) frequencies, which in several studies have been predictive of graft-versus-host disease (GVHD). Recently high anti-recipient IL-4 producing HTLp frequencies have been reported and associated with a decreased risk of GVHD. The aim of the present study was to define the optimal conditions for combined determination of IL-2 and IL-4 producing anti-recipient HTLp frequencies. We have optimised the CT.h4S bioassay with regards to specificity, sensitivity, detection limit, and reproducibility. We have found the optimal assay conditions to be 1 x 10 (4) CT.h4S cells/well deprived of IL-4 for 24 h and preincubated for 7 h followed by 18 h of incubation with tritiated methyl-thymidine. In this setting the CT.h4S bioassay detects 5 pg/ml of human recombinant IL-4 with no detection of IL-2 in concentrations below 500 pg/ml. We have found 72 h of culture optimal for detection of IL-2 and IL-4 produced by human mononuclear cells (MNC) in response to stimulation with phytohaemaglutinin and for detection of IL-2 in human leukocyte antigen (HLA)-mismatched mixed leukocyte culture (MLC). An interindividual variation in cytokine accumulation was demonstrated for IL-4 but not for IL-2. With the use of 5x10(4) responder cells/well no IL-4 could be detected in HLA-mismatched MLC between days 1 and 16. The lack of IL-4 detection was not due to high amounts of soluble IL-4 receptor. With the use of 1x10(6) responder cells/well in HLA-mismatched MLC, we found limited IL-4 accumulation still increasing at day 12. We conclude that the CT.h4S bioassay is a reliable and specific method for quantification of IL-4 accumulation in cultures of human MNC. The difference in optimal timing for IL-2 (day 3) and IL-4 (>/=day 12) detection and evidence of very low IL-4 producing HTLp frequencies makes the relevance of a combined IL-2/IL-4 HTLp assay questionable.     

GLUT-4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study

In whole muscle homogenates, the glucose transporter-4 (GLUT-4) content is reported to be higher in muscles consisting predominantly of oxidative (type-1) muscle fibres than in muscles consisting predominantly of glycolytic (type-2) fibres. From these findings, it has been deduced that in rat muscle, oxidative fibres have an intrinsically higher level of GLUT-4 protein than glycolytic fibres. No data is available concerning human muscle. Moreover, the fibre-type-specific expression of GLUT-4 has not yet been examined directly. In this study, the relative abundance of GLUT-4 protein expression in individual fibres of different types within a muscle was compared directly in immunohistochemical assays. The human vastus lateralis muscle and a selection of rat muscles were studied using a novel GLUT-4 antiserum. It is concluded that the pattern of fibre-type-specific GLUT-4 expression differs between human and rats and varies between the different muscles studied, indicating that non-fibre-type-specific factor(s) affect expression of GLUT-4. The observation that within a muscle a fibre-type-specific expression of GLUT-4 was observed indicates that fibre-type-specific factors contribute to GLUT-4 expression as well. Thus, it can be postulated that both fibre-type-dependent and fibre-type-independent factors affect GLUT-4 expression.     

Influence of pH and pCO2 on Alpha-Receptor Mediated Contraction in Brain Vessels

The response of isolated brain vessels to various pH levels or carbon dioxide tensions was analyzed. Reduction of the pH induced a slight relaxation of the vessel, whereas an increase in the pH produced a slight contraction. These effects were markedly exaggerated when the alpha-adrenergic receptors in the vascular wall were activated by noradrenaline. During these conditions the contractile response to noradrenaline was reduced by about 40 per cent at a pH of 7.01, while, on the other hand, the response was enhanced 3-fold at a pH of 7.80. Variations in carbon dioxide tension of the buffer solution between 16 mmHg and 64 mmHg produced no consistent change, provided the pH remained constant. The results indicate that an interaction between the perivascular pH and the adrenergic alpha-receptor mediated contraction in brain vessels may occur.