Novel and de novo mutations of the IRF6 gene detected in patients with Van der Woude or popliteal pterygium syndrome

The interferon regulatory factor 6 gene (IRF6) has been identified as the major Van der Woude (VWS) syndrome and popliteal pterygium (PPS) syndrome gene with mutations in the majority of the kindreds. We have studied altogether 17 kindreds from Sweden, Finland, Norway, Thailand and Singapore, and report here 10 mutations, six of them previously unseen. In two kindreds, we could document de novo mutations, both of them changing a codon for a glutamine residue to a stop. No mutation could be detected in the four VWS kindreds from Finland, suggesting a founder effect for a mutation in an atypical noncoding position. Our findings demonstrate that several distinct mutations occur in the Swedish population, and confirm the general notion of a broad spectrum of IRF6 mutations underlying the VWS/PPS phenotypes.     

Parametric renal blood flow imaging using [<Superscript>15</Superscript>O]H<Subscript>2</Subscript>O and PET

Purpose  The quantitative assessment of renal blood flow (RBF) may help to understand the physiological basis of kidney function and allow an evaluation of pathophysiological events leading to vascular damage, such as renal arterial stenosis and chronic allograft nephropathy. The RBF may be quantified using PET with H₂ ¹⁵O, although RBF studies that have been performed without theoretical evaluation have assumed the partition coefficient of water (p, ml/g) to be uniform over the whole region of renal tissue, and/or radioactivity from the vascular space (V _A. ml/ml) to be negligible. The aim of this study was to develop a method for calculating parametric images of RBF (K ₁, k ₂) as well as V _A without fixing the partition coefficient by the basis function method (BFM). Methods  The feasibility was tested in healthy subjects. A simulation study was performed to evaluate error sensitivities for possible error sources. Results  The experimental study showed that the quantitative accuracy of the present method was consistent with nonlinear least-squares fitting, i.e. K _1,BFM=0.93K _1,NLF−0.11 ml/min/g (r=0.80, p<0.001), k _2,BFM=0.96k _2,NLF−0.13 ml/min/g (r=0.77, p<0.001), and V _A,BFM=0.92V _A,NLF−0.00 ml/ml (r=0.97, p<0.001). Values of the Akaike information criterion from this fitting were the smallest for all subjects except two. The quality of parametric images obtained was acceptable. Conclusion  The simulation study suggested that delay and dispersion time constants should be estimated within an accuracy of 2 s. V _A and p cannot be neglected or fixed, and reliable measurement of even relative RBF values requires that V _A is fitted. This study showed the feasibility of measurement of RBF using PET with H₂ ¹⁵O.     

Ligation of ameroid-stenosed coronary artery leads to reproducible myocardial infarction--a pilot study in a porcine model

OBJECTIVE: Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described. MATERIALS AND METHODS: Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed 1 to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining. RESULTS: LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 +/- 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas. CONCLUSIONS: This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies.     

Mammal‐Derived Respiratory Lipocalin Allergens do not Exhibit Dendritic Cell‐Activating Capacity

Most mammal‐derived respiratory allergens belong to the lipocalin family of proteins. Determinants of their allergenic capacity are still unknown. Innate immune cells, in particular dendritic cells, have been shown to be involved in the allergenicity of some proteins. As recognition by dendritic cells is one of the few plausible mechanisms for the allergenicity of proteins, we wanted to investigate their role in the allergenicity of lipocalin allergens. Therefore, we first incubated human monocyte‐derived dendritic cells with immunologically functional recombinant allergens mouse Mus m 1, dog Can f 1 and 2, cow Bos d 2, horse Equ c 1 and natural Bos d 2. Then, the surface marker expression and cytokine production of dendritic cells and their capacity to promote T cell proliferation and Th2 immune deviation in naïve CD4⁺ T cells were examined in vitro. We found that near to endotoxin‐free lipocalin allergens had no effect on the activation, allostimulatory capacity or cytokine production of dendritic cells. The dendritic cells could not induce immune deviation in naïve CD4⁺ T cells. In contrast, lipopolysaccharide activated the dendritic cells efficiently. However, lipocalin allergens were not able to modify the lipopolysaccharide‐induced responses. We conclude that an important group of mammal‐derived respiratory allergens, lipocalins, appear not to be able to activate dendritic cells, a major component involved in the allergenicity of some proteins. It is conceivable that this incapacity of lipocalin allergens to arouse innate immunity may be associated with their poor capacity to induce a strong T cell response, verified in several studies.     

Using magnetoencephalography in assessing auditory skills in infants and children.

In this paper, the use of magnetoencephalography (MEG) in studying the basic auditory skills in infants and children is reviewed. The auditory skills are related to perceiving sound onsets and offsets of sounds, extracting rules and regularities in sound environments, perceiving differences and changes in sounds, categorizing sound elements, allocating attention towards certain sounds or sound streams, and attaching semantic information into sounds. Studying each of these auditory skills with MEG in particular stimulation paradigms is shortly reviewed, including two examples of data sets in children.     

Cephalometric pharyngeal changes after Le Fort I osteotomy in different types of clefts.

Fifty patients with clefts (30 unilateral cleft lip and palate (UCLP), 9 bilateral cleft lip and palate (BCLP), and 11 cleft palate only (CP), mean age 25 years) treated with Le Fort I osteotomy were compared retrospectively from cephalograms taken shortly before operation, and at six months and one year postoperatively. Patients with bimaxillary surgery or previous velopharyngoplasty, or both, were excluded. Maxillary advancement was moderate in all groups. One year postoperatively there was a significant change (73%-90% of the surgical advancement) in the sagittal depth of the nasopharyngeal airway but not in the depth of the oropharyngeal airway, the length of the soft palate or the position of the hyoid bone. The nasopharyngeal airway was largest in the CP group both preoperatively and postoperatively. Eleven patients (7 CP, 4 UCLP) had a velopharyngoplasty after the osteotomy to improve their speech. There was no difference in the nasopharyngeal airway in the patients treated by velopharyngoplasty compared with those not so treated, but they seemed to have the shortest maxillas and the greatest surgical changes vertically.     

Pinhole osteotomy in distraction osteogenesis - a technical note.

A new surgical approach for performing the mandibular osteotomy for distraction osteogenesis is described. In order to minimize trauma to bone caused by the osteotomy - and adjacent soft tissue - caused by excessive stretching - an additional transbuccal pinhole incision is made. The shaft of the saw blade is passed through this incision. This allows a precise cut of the mandibular ramus at the planned angle and easy guidance of the saw during the procedure. The method can be used both with extraoral or intraoral distraction devices in children and adults.     

Comparison of MRI and positron emission tomography for measuring myocardial perfusion reserve in healthy humans.

Myocardial perfusion reserve (MPR, defined as the ratio of the maximum myocardial blood flow (MBF) to the baseline) is an indicator of coronary artery disease and myocardial microvascular abnormalities. First-pass contrast-enhanced magnetic resonance imaging (CE-MRI) using gadolinium (Gd)-DTPA as a contrast agent (CA) has been used to assess MPR. Tracer kinetic models based on compartmental analysis of the CA uptake have been developed to provide quantitative measures of MBF by MRI. To study the accuracy of Gd-DTPA first-pass MRI and kinetic modeling for quantitative analysis of myocardial perfusion and MPR during dipyridamole infusion, we conducted a comparison with positron emission tomography (PET) in 18 healthy males (age = 40 +/- 14 years). Five planes were acquired at every second heartbeat with a 1.5T scanner using a saturation recovery turboFLASH sequence. A perfusion-related parameter, the unidirectional influx constant (Ki), was computed in three coronary artery territories. There was a significant correlation for both dipyridamole-induced flow (0.70, P = 0.001) and MPR (0.48, P = 0.04) between MRI and PET. However, we noticed that MRI provided lower MPR values compared to PET (2.5 +/- 1.0 vs. 4.3 +/- 1.8). We conclude that MRI supplemented with tracer kinetic modeling can be used to quantify myocardial perfusion.