Familial partial trisomy 5p resulting from segregation of an insertional translocation

A case of duplication of segment p13-p15 of the short arm of chromosome 5 as the result of an insertional translocation in a mentally retarded girl with congenital anomalies is reported. Some of the apparently balanced carriers of the inverted insertion showed minor congenital anomalies.     

Effects of HDL3 on the expression of matrix-degrading proteases in human endothelial cells

Modified lipoproteins have been suggested to modulate the expression of matrix-degrading proteases in the vascular wall. Since oxidized high density lipoprotein (HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the role of native and oxidized HDL3 on the expression of 35 proteases and their inhibitors in human endothelial cells using microarray analysis. Matrix metalloproteinase (MMP)-1, -2, -10, -13 and -14, tissue inhibitor of MMP (TIMP)-1, -2 and -3, cathepsin B and D, and cystatin C were expressed under basal conditions, of which MMP-10 and cystatin C expression have not been described before in endothelial cells. Native HDL3 increased MMP-1 and MMP-14 expression and decreased MMP-13 expression, whereas oxidized HDL3 increased PAI-1 and MMP-1 expression. The expression pattern was confirmed by quantitative real-time PCR. In summary, a large repertoire of matrix-degrading proteases is expressed in endothelial cells, an expression that can be modulated by native and oxidized HDL3.     

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.     

Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.     

IgVH gene analysis suggests that peritoneal B cells do not contribute to the gut immune system in man

The contribution of peritoneal B cells to the intestinal lamina propria plasma cell population is well documented in mice, but unknown in humans. We have analyzed immunoglobulin (Ig) genes of human peritoneal B cells, because such genes show distinctive characteristics in mucosal B cells, particularly highly mutated variable regions. Here, we report the characteristics of variable region genes used by IgM, IgA and IgG in peritoneal cells. We focused on the properties of IgV(H)4-34 to allow comparisons of like-with-like between different isotypes and cells from different immune compartments. We observed that the IgM genes were mostly unmutated, and that the mutated subset had less mutations than would be expected in a mucosal B cell population. Likewise, the IgV(H)4-34 genes used by IgA and IgG from peritoneal B cells had significantly lower numbers of mutations than observed in the mucosal counterparts. Other trends observed, while not reaching statistical significance, followed the trend of peripheral B cells. The peritoneal B cell population had more IgA1 than IgA2 sequences, and there was no dominance of J(H)4 in the IgA from peritoneum or spleen, in contrast to the mucosal sequences. Overall, this study suggested that human peritoneal B cell are either peripheral or mixed in origin; they are unlikely to represent an inductive compartment for the mucosal B cell system.     

Electronic patient-provider communication: will it offset office visits and telephone consultations in primary care?

BACKGROUND AND AIM: Electronic patient-provider communication promises to improve efficiency and effectiveness of clinical care. This study aims to explore whether a secure web-based messaging system is an effective way of providing patient care in general practices. METHOD: We conducted a randomised controlled trail and recruited 200 patients from the waiting area in one primary clinic in Norway. Participants were randomised to either the intervention group, which received access to a secure messaging system, or the control group receiving standard care without such access. Primary outcome measures were number of online consultations, telephone consultations and office visits in the two groups. Data were derived from patient records and collected 1 year prior to (baseline), and 1 year after the intervention. RESULTS: Forty-six percent of the patients who were given access to the messaging system (n=99) used the online communication system on at least one occasion (ranging from 1 to 17 messages per patient per year). A total of 147 electronic messages were sent to six general practitioners during a 1-year trial period. Eleven percent of the messages were to schedule an appointment. In 10% of the messages, the GP was unable to respond adequately and recommended an office visit. The reduction in office visits over time was greater for the intervention group than for the control group (P=0.034). There was however no significant difference in the number of telephone consultations between the groups during the study (P=0.258). CONCLUSION: The use of a secure electronic messaging system reduced the number of office visits at the general practice, but not phone consultations.     

Desensitization of acetylcholine induced inositol 1,4,5-trisphosphate formation in neuroblastoma SH-SY5Y cells following repetitive acetylcholine stimulations

In this study, the desensitization of acetylcholine-induced inositol 1,4,5-trisphosphate [I(1,4,5)P₃] formation, upon short-time prestimulations, was investigated in cultures of human neuroblastoma SH-SY5Y cells. Four repeated stimulations for 10 seconds with 10 μM acetylcholine were necessary to induce a desensitization of the I(1,4,5)P₃ formation. The desensitization was observed 4 hours after the initiation of repetitive stimulations. The same effect was obtained by a single prestimulation with 1 mM acetylcholine. Preincubation of the cells with phorbol 12-myristate 13-acetate (PMA) markedly down-regulated the acetylcholine-induced I(1,4,5)P₃ formation. However, the protein kinase C (PKC) inhibitors H7 and staurosporine did not influence the desensitization induced by four repeated stimulations with 20 μM acetylcholine. These results indicate that the signal transduction can be desensitized following repeated stimulations with sub-maximal concentrations of receptor agonist and although activation of PKC can induce the same down-regulation, PKC is most likely not involved in the desensitization induced by repetitive acetylcholine-stimulations.     

Meiotic and cytoplasmic maturation of oocytes collected in stimulated cycles is asynchronous

Oocytes collected in stimulated cycles are more readily fertilizedafter preincubation than are oocytes inseminated immediatelyafter collection. It has not been ascertained, however, whetherthis increase in the fertilization rate is due to extrusionof the first polar body (meiotic maturation) during this period,or to some conclusive cytoplasmic maturation subsequent to thepolar body extrusion. When analysing oocytes with a polar body(n = 14) by transmission electron microscopy, differences wereobserved in the appearance of cytoplasmic features which werecorrelated to the total durations both of systemic human chorionicgonadotrophin influence before collection and of oocyte culture.These differences were manifested as a delayed formation inaggregates of the smooth endoplamic reticulum in the ooplasmof oocytes having a polar body and might have signified a cytoplasmicmaturation. The degree of synchrony in the oocytes varied andthis could explain why some oocytes can be fertilized when inseminatedshortly after collection and others not until 8 h or even moreafter collection. Thus, although meiotic and cytoplasmic maturationis likely to be synchronized at ovulation of an oocyte in anatural cycle, they appear to be mainly asynchronous in oocytescollected in stimulated cycles.     

Enzyme-Linked Immunosorbent Assay for Determination of Major Excrement Allergens of House Dust Mite Species D. pteronyssinus, D. farinae and D. microceras

Species-specific enzyme-linked immunosorbent assays (ELISA) for major excrement allergens (Dp42, Df6 and Dm6) of D. pteronyssinus, D. farinae and D. microceras in house dust were established, using immunoabsorbed, monospecific rabbit antibodies, coupled to horse radish peroxidase. The limit of detection was 13, 4 and 38 ng/ml, respectively. The coefficient of variation for the entire procedure, including dust sieving (212 micron) and extraction was 5-16% for allergen levels above 1000 ng/g dust. Allergen concentration by ELISA correlated well with the number of mite bodies identified and counted by microscopy in 31 dusts (r = 0.88, 0.86 and 0.82 for combined Dermatophagoides sp., D. pteronyssinus and D. farinae group, resp.) Dermatophagoides allergen was recorded in 21/22 mattress dusts (median: 26,000 ng/g; maximum: 290,000 ng/g). D. pteronyssinus allergen occurred in largest amounts (median 7,500 ng/g) followed by D. microceras (median 650 ng/g) and D. farinae (median 240 ng/g).