Comparative genetic isolation patterns for multiple headwater fishes in three geographic regions.

Headwater-resident fishes may be prone to a high rate of isolation and a pronounced hierarchical genetic structure due to a combination of niche preference and dendritic effects of river networks. Genetic isolation patterns were compared using microsatellites in six headwater fishes, Fundulus olivaceus, Semotilus atromaculatus, Erimyzon claviformis, Etheostoma artesiae, Etheostoma whipplei and Etheostoma parvipinne, in three geographic regions that included drainages of small, medium and large sizes in the southern United States. All species showed hierarchical nesting of genetic populations and there were clear and mostly consistent differences between species and regions that were identified through summary statistics derived from two independent analyses. For species comparisons, a high isolation grouping (increased number of isolated genetic clusters or sites within regions) and a low-isolation grouping (decreased number of clusters or sites) were identified. Species group placement was related to niche breadth along the river continuum and presumed abundance and variability of preferred microhabitats, with increased headwater specialization among species being associated with placement in the high-isolation grouping. There was a weakly significant positive effect of drainage size on the number of isolated clusters or sites across all species. Regional patterns were shared in two species, with the region containing the smallest drainages having lower rates of isolation in both datasets. This study shows the effects of regional and species characteristics on genetic isolation for headwater species, which are especially prone to isolation due to spatial, dendritic effects of river networks.

Pediatric Oncologic Imaging: A Key Application of Combined PET/MRI.

UNLABELLED: Pediatric imaging has been identified as a key application of combined whole-body PET/MRI. First studies have revealed the clinical feasibility and possible advantages of PET/MRI over PET/CT and MRI. Besides a significant reduction in radiation exposure of about 50 - 75 %, combined whole-body PET/MRI offers the diagnostic advantage of the multiparametric characterization of pathophysiologic processes and helps reduce the number of necessary imaging studies. However, very few studies focusing on pediatric PET/MRI have been published to date. Additional studies are necessary in order to fully appreciate the clinical impact of this novel method. This review article shall summarize the existing literature concerning pediatric PET/MRI and give insight into the practical experience derived from over 160 pediatric PET/MRI examinations that were performed in Tübingen. KEY POINTS: •Combined PET/MR is a promising imaging modality in pediatric oncology. •Using combined PET/MRI, diagnostic radiation exposure of pediatric patients and the number of necessary imaging studies can be reduced. •Further clinical studies are necessary in order to define specific indications for combined PET/MRI in pediatric radiology.

Isolation and characterization of microsatellite loci for the blackstripe topminnow Fundulus notatus and their variability in two closely related species.

A total of 17 polymorphic microsatellite loci were isolated from the blackstripe topminnow Fundulus notatus. In a sample of 29 individuals, these loci were found to possess two to 19 alleles with expected heterozygosity values ranging from 0.212 to 0.919 and all but one of the loci conformed to Hardy-Weinberg equilibrium expectations. Many of these loci were polymorphic in the closely related species Fundulus olivaceus and Fundulus euryzonus providing a set of markers that should prove useful in future ecological and evolutionary studies of members of this species complex.

[CT-guided radiofrequency (RF) ablation of osteoid osteoma: clinical long-term results]. / CT-gesteuerte Radiofrequenz (RF)-Ablation von Osteoidosteomen: klinische Langzeitergebnisse.

PURPOSE: To evaluate CT-guided radiofrequency (RF) ablation of osteoid osteoma using internally cooled monopolar RF electrodes for technical success, complications and clinical long-term success. MATERIALS AND METHODS: Between April 1999 and July 2006, 23 patients were treated under general anesthesia with CT-guided RF ablation using an internally cooled monopolar single RF electrode (Cool-tip, Valleylab, TycoHealthcare, Boulder, USA; active tip: 10 mm). For the removal of the nidus, we used either a manual or an automated drill. The technical success was evaluated by a CT scan (MSCT, Siemens Medical Solutions, Forchheim). The clinical long-term success was investigated by questioning patients prior to discharge, and after 6, 12 and 18 months. After 18 months, patients were interviewed on an annual basis. RESULTS: The technical success rate was 100 %. The nidus was located in n = 19 cases at the lower extremity and in n = 4 cases at the upper extremity. Minor complications were observed for n = 2 patients. The mean hospitalization time was 1.5 d (1-2 d). The mean follow-up was 75.9 months (18-120 months) for n = 23 patients. No local recurrence was observed. One patient had intermediate pain one week after RF ablation without recurrent symptoms. CONCLUSION: CT-guided RF ablation using an internally cooled monopolar single RF electrode is an effective and safe minimally invasive method for the treatment of osteoid osteoma with excellent clinical long-term success.

[Whole-body MRI in children and juveniles]. / Ganzkörper-MRT bei Kindern und Jugendlichen.

The imaging of systemic disorders without radiation exposure by whole-body MRI (wb-MRI) represents a paradigm shift for pediatric radiology. The reduction of multiple regional examinations, if necessary under sedation, results in a faster treatment start. Modern scanner techniques using automatic table movement and allowing the combination of multiple coil elements and synchronized signal recording with numerous independent receiving channels are the basic prerequisite for high-resolution wb-MRI. The main indications are the evaluation of multifocal bone involvement in different disorders, rheumatic disorders including fever of unknown origin or metastatic spread in solid tumors. Based on the research, there is currently no absolute indication. However, wb-MRI has been shown to yield a higher diagnostic performance than bone scintigraphy and comparable results to FDG-PET for the detection of bone metastases. Due to the low number of published studies, it is uncertain for which entity of solid tumors wb-MRI is the modality of choice and for which tumors wb-MRI will play only a complementary role in the diagnostic work-up. Methodical strategies, pitfalls in image analysis, indications and diagnostic accuracy will be discussed based on already published results as well as our own experience from over 400 examinations, thus providing an overview of the recent research as well as supplying relevant aspects of the daily routine in pediatric wb-MRI.

A new species of Profundulus (Cyprinodontiformes: Profundulidae) from the Honduran central highlands.

A new species of Profundulus, Profundulus portillorum, from the Honduran central highlands is described. Profundulus portillorum belongs to the Profundulus labialis species group and is distinct from the Profundulus punctatus species group in that it lacks a humeral spot and less than half of the caudal fin is scaled. Within the P. labialis species group, P. portillorum has a more slender body, smaller eye, fewer anal rays, caudal rays and lateral-line scales than other species. Forty-one specimens were collected around emergent vegetation in the margins of two small (2-5 m in width, 20-40 cm in depth), high-elevation (1300 m) tributaries of the Río Calam within the Río Ulúa drainage. These specimens represent the easternmost collection of any Profundulus and the first collection of any member of the P. labialis species group from Honduras.

[Reproducibility of readings of ISO C 3D and CT lumbar pedicle screw scans]. / Reproduzierbarkeit der Befundung von lumbalen Pedikelschraubenpositionen mit ISO C 3D und CT.

PURPOSE: This study was conducted to evaluate the reproducibility of the reading of lumbar pedicle screw scans using a C-arm-based imaging system in comparison to computed tomography. The influence of the technique and the experience of the rater should be determined. MATERIALS AND METHODS: The lumbar spines of 23 patients were stabilized using 102 pedicle screws. The position of the screws was controlled intraoperatively using an Arcadis Orbic 3D scanner. All scans were evaluated independently by three raters. The position of the implants in reference to the pedicle walls was described. Additionally, another 100 lumbar pedicle screws in 16 patients were evaluated postoperatively with a multirow CT. Kappa according to Fleiss was calculated for the reproducibility of the rater statements. Each rater repeated the analysis of 24 screws to assess the intraobserver variance. RESULTS: The reports of the CT scans showed significantly less variation. The consent of all 3 raters was achieved in 79.4 vs. 65.1 % of cases. The Kappa values were 0.56 and 0.29, respectively. Poor results were obtained especially for the medial pedicle wall (consent 70.0 vs. 50.0 %). The influence of the experience of the rater was not able to be verified. CONCLUSION: The image quality of the ISO C 3D is worse than that of multirow CT scans for the evaluation of lumbar pedicle screws. This causes greater variance among the rater reports. We stopped using the ISO C 3D technique intraoperatively for the implantation of lumbar pedicle screws.

[Dynamic magnetic resonance nephrography and urography of uropathies in children]. / Dynamische Magnetresonanz-Nephrografie und -Urografie bei Kindern mit Harnwegserkrankungen.

PURPOSE: To evaluate an improved method of dynamic magnetic resonance (MR) nephrography with short acquisition time and compensation of breathing motion for assessment of renal excretion and split renal function in children with anomalies of the urinary tract. MATERIALS AND METHODS: A protocol for dynamic MR nephrography was implemented using a T1-weighted navigator-gated TurboFLASH sequence (TR/TE 498 ms/1.25 ms, saturation recovery time 300 ms, flip angle 8 degrees ). After bolus injection of 0.05 mmol/kg gadolinium dimeglumine (Gd-DTPA), split renal function was determined from the contrast-medium excretion. In 20 patients (ages between 3 months and 14 years), dynamic MR nephrography and MAG3 radionuclide scintigraphy as the gold standard were performed. RESULTS: In all children, T1-weighted images were able to be recorded over 40 minutes at a nearly identical diaphragm position using the TurboFLASH sequence, thus allowing for exact region-of-interest analysis of the excretion and split renal function. The course of the contrast-medium concentration was able to be measured in the renal pelvis with good accuracy due to the high spatial resolution and the lack of breathing artifacts. Excellent correlation to the MAG3 scintigraphy was demonstrated for the excretion and split renal function (correlation coefficient: 0.975). CONCLUSION: Dynamic MR nephrography allows for reliable assessment of renal function in children with anomalies of the urinary tract with higher spatial resolution as compared to radionuclide scintigraphy.

Hybridization and reproductive isolation among syntopic populations of the topminnows Fundulus notatus and F. olivaceus.

Fundulus notatus and Fundulus olivaceus are two closely related topminnow species that exhibit similar ecological niches and broad, largely overlapping, North American ranges extending throughout much of the Mississippi River drainage as well as the coastal drainages of the Gulf of Mexico. Previous studies have suggested that these two species are reproductively compatible despite cytogenetic differences and will hybridize when syntopic. We used nuclear and mtDNA loci to assess levels of hybridization and test for introgression in syntopic populations of these two species in four drainages in southern Illinois. Although hybridization was detected in all syntopic populations, an assessment of the proportion of hybrid individuals indicated a deficiency of hybrids relative to expectations under random mating. We determined that, although mtDNA introgression was prevalent and extended beyond the zones of contact, evidence of nuclear introgression was limited to the zone of sympatry.

FGF signaling antagonizes cytokine-mediated repression of Sox9 in SW1353 chondrosarcoma cells.

OBJECTIVE: The Sox9 transcription factor has emerged as an important determinant of chondrocyte differentiation, including the regulation of type II collagen (Col2) and aggrecan gene expression. We sought to identify a human cell line model that conserves the Sox9 regulatory pathways identified in the mouse. DESIGN: The SW1353 chondrosarcoma cell line was considered to be a candidate for Sox9 studies. The activity of a Sox9 regulated Col2a1 enhancer reporter gene was analyzed in response to treating cells with known regulators of murine Sox9 expression/activity. The effect of treatment on expression of the endogenous Sox9 gene was analyzed by real-time PCR and Western blot. RESULTS: Col2 enhancer activity was stimulated by fibroblast growth factors (FGF-1 and -2) and repressed by inflammatory cytokines (IL-1beta and TNFalpha) in SW1353 cells. These effects correlated with changes in Sox9 mRNA and protein levels. In addition, FGF-9 was shown to stimulate enhancer activity and Sox9 expression. Cotreatment studies demonstrated that FGFs functionally antagonize the cytokine-mediated repression of Sox9 expression and Col2 enhancer activity. CONCLUSIONS: SW1353 cells represent a useful human cell model as they conserve many Sox9 signaling pathways previously demonstrated in mouse chondrocytes. We identify FGF-9 as a particularly potent Sox9 agonist. The antagonism between FGFs and cytokines on Sox9 expression and Col2 enhancer activity suggests that Sox9 integrates the opposing activities of FGFs and cytokines. We also find that SW1353 cells respond to very low doses of IL-1 with Col2 enhancer activation, while increasing doses lead to repression.

Synergistic effect between iron and gadolinium in MRI.

Different combinations of iron glycerophosphate (Fe) and gadolinium-diethylene triamine pentaacetic acid (DTPA) (Gd) were imaged with a three-dimensional (3D) gradient-recalled echo (GRE), a 2D GRE, and a HASTE sequence on a 1.5-T MR scanner. A combination of Fe and Gd results in a synergistic effect, which improves the signal gain for selective 3D imaging of the colon and simultaneously decreases the endoluminal signal on the HASTE and 2D GRE images for better visualization of water and Gd-enhanced structures in the gut wall.

Inhibition of protein phosphatase 1 decreases PTH secretion from isolated dispersed parathyroid cells.

To investigate the regulation of parathyroid hormone secretion by phosphatases we examined the effect of okadaic acid, a selective inhibitor of protein phosphatases (PP)-1 and -2A, on isolated, dispersed parathyroid cells. Okadaic acid inhibited secretion from intact bovine, intact human and streptolysin-O permeabilized bovine cells. Approximately 10(-6) M okadaic acid resulted in a 50% decrease in parathyroid hormone (PTH) secretion from both intact and permeabilized cells, consistent with PP-1 being the target of inhibition. Upon subcellular fractionation, PP-1 overlapped but was not identical to either PTH, a marker of the secretory granule, or Na+/K+-ATPase, a plasma membrane marker. In summary, PP-1 activity is involved in Ca2+-dependent but not basal PTH secretion.

Reconstitution of calcium-regulated parathyroid hormone secretion from streptolysin-O-permeabilized parathyroid cells by guanosine 5'-O-(thio)triphosphate.

Intracellular Ca2+ levels determine the amount of PTH secretion from parathyroid cells. Dissociated calf parathyroid cells were permeabilized with streptolysin-O (SLO) to provide an in vitro model system to examine Ca(2+)-dependent regulation of hormone secretion. PTH release from these cells was energy dependent and increased by cytosolic cofactors. Guanosine 5'-O-(thio)triphosphate (GTP gamma S) increased PTH secretion from SLO-permeabilized cells in a dose-dependent manner from 0.1-100 microM. In the absence of GTP gamma S there was no relationship between the ambient Ca2+ concentration and the rate of PTH secretion. However, in the presence of GTP gamma S, intracellular Ca2+ inhibited PTH secretion with an EC50 of approximately 0.1 microM, corresponding to physiological intracellular Ca2+ levels. Thus, the addition of GTP gamma S to SLO-permeabilized parathyroid cells reconstituted the inverse relationship between extracellular Ca2+ and PTH secretion that is observed in vivo and in intact cells. The data indicate that this effect is mediated at least in part by heterotrimeric guanosine triphosphatases. In addition, calcium/calmodulin-dependent protein kinase II appears to mediate low Ca(2+)-dependent PTH secretion from these cells.

Clinical investigations: taking a global approach, part I.

Clinical investigations are a vital part of the development process of a medical device. A number of advantages can be gained by initiating a global approach to clinical investigation and implementing a well-designed, multinational, multicentred programme. It can mean that market approval can be accelerated and that the marketing effort is supported in specific countries, which can lead to greater market share. This article, which will be published in two parts, outlines the strategy that is required to set up and implement an effective global clinical investigation. Part I considers the elements that are involved and defines the advantages of adopting this approach.

Characterization of cAMP-dependent protein kinase activation by CCK in rat pancreas.

This study reports on the use of a new sensitive assay of cAMP-dependent protein kinase activity to examine the effect of cholecystokinin (CCK) on the cAMP second messenger cascade in rat pancreatic acini. Treatment of acini with both low (pM) and high (nM) concentrations of CCK was associated with an increase in cAMP-dependent protein kinase activity. The increases in kinase activity were detected in the absence of phosphodiesterase inhibition, a condition required to detect a measurable increase in cellular cAMP in these cells. Furthermore, the cAMP cascade was dissociated from the secretory effects of CCK, since the CCK analogue, OPE, mediates enzyme secretion but does not increase cellular cAMP levels or kinase activity.

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome.

A 38-year-old black man died from acquired immunodeficiency syndrome (AIDS) after a 15-month course. The autopsy revealed a pancolitis and a pneumonia caused by cytomegalovirus (CMV). Exceptionally, there also was a periventricular encephalitis caused by the same organism. Identification of the virus was aided by immunoperoxidase methods.