DCE-MRI of the breast in a stand-alone setting outside a complementary strategy - results of the TK-study.

OBJECTIVES: To evaluate the accuracy of MRI of the breast (DCE-MRI) in a stand-alone setting with extended indications. MATERIALS AND METHODS: According to the inclusion criteria, breast specialists were invited to refer patients to our institution for DCE-MRI. Depending on the MR findings, patients received either a follow-up or biopsy. Between 04/2006 and 12/2011 a consecutive total of 1,488 women were prospectively examined. RESULTS: Of 1,488 included patients, 393 patients were lost to follow-up, 1,095 patients were evaluated. 124 patients were diagnosed with malignancy by DCE-MRI (76 TP, 48 FP, 971 TN, 0 FN cases). Positive cases were confirmed by histology, negative cases by MR follow-ups or patient questionnaires over the next 5 years in 1,737 cases (sensitivity 100 %; specificity 95.2 %; PPV 61.3 %; NPV 100 %; accuracy 95.5 %). For invasive cancers only (DCIS excluded), the results were 63 TP; 27 FP; 971 TP and 0 FN (sensitivity 100 %; specificity 97.2 %; PPV 70 %; NPV 100 %; accuracy 97.5 %). CONCLUSION: The DCE-MRI indications tested imply that negative results in DCE-MRI reliably exclude cancer. The results were achieved in a stand-alone setting (single modality diagnosis). However, these results are strongly dependent on reader experience and adequate technical standards as prerequisites for optimal diagnoses. KEY POINTS: • DCE-MRI of the breast has a high accuracy in finding breast cancer. • The set of indications for DCE-MRI of the breast is still very limited. • DCE-MRI can achieve a high accuracy in a 'screening-like' setting. • Accuracy of breast DCE-MRI is strongly dependent on technique and reader experience. • A negative DCE-MRI effectively excludes cancer.

Leiomyosarcoma of the inferior vena cava extending into the right atrium. A rare differential diagnosis of a right atrial tumor with fatal outcome.

A 54-year-old female patient presented with a progressive and deteriorating dyspnea at the slightest exertion in particular during the past few days before presentation. Transthoracic echocardiography revealed a large space-occupying lesion in the right atrium extending into the inferior vena cava (IVC). Abdominal magnetic resonance aortography showed an elongated space-occupying lesion in the IVC with a significant portion of the tumor and almost completely filling the right atrium accompanied by an infiltration of the hepatic and renal veins. A pronounced tumor infiltration of the IVC at the level of the liver was confirmed intraoperatively and immunohistochemical analysis showed a moderate to poorly differentiated leiomyosarcoma. The extended tumor was successfully removed by a complex operation of the thorax and abdomen but the procedure was accompanied by severe bleeding. A few hours following the procedure the patient died due to a further episode of irreversible intra-abdominal hemorrhage.

Covalently linked immunomagnetic separation/adenosine triphosphate technique (Cov-IMS/ATP) enables rapid, in-field detection and quantification of Escherichia coli and Enterococcus spp. in freshwater and marine environments.

AIMS: Developing a rapid method for detection of faecal pollution is among the critical goals set forth by the Environmental Protection Agency in its revision of water quality criteria. The purpose of this study is to devise and test covalently linked antibody-bead complexes for faecal indicator bacteria (FIB), specifically Escherichia coli or Enterococcus spp., in measuring water quality in freshwater and marine systems. METHODS AND RESULTS: Covalently linked complexes were 58-89% more robust than antibody-bead complexes used in previous studies. Freshwater and marine water samples analysed using covalently linked immunomagnetic separation/adenosine triphosphate quantification technique (Cov-IMS/ATP) and culture-based methods yielded good correlations for E. coli (R = 0·87) and Enterococcus spp. (R = 0·94), with method detection limits below EPA recreational water quality health standards for single standard exceedances (E. coli- 38 cells per 100 ml; Enterococcus spp. - 25 cells per 100 ml). Cov-IMS/ATP correctly classified 87% of E. coli and 94% of Enterococcus spp. samples based on these water quality standards. Cov-IMS/ATP was also used as a field method to rapidly distinguish differential loading of E. coli between two stream channels to their confluence. CONCLUSIONS: Cov-IMS/ATP is a robust, in-field detection method for determining water quality of both fresh and marine water systems as well as differential loading of FIB from two converging channels. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first work to present a viable rapid, in-field assay for measuring FIB concentrations in marine water environments. Cov-IMS/ATP is a potential alternative detection method, particularly in areas with limited laboratory support and resources, because of its increased economy and portability.

Incidental non-secreting adrenal masses in cancer patients: intra-individual comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography with computed tomography and shift magnetic resonance imaging.

The ability of integrated (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated. Visual interpretation, tumour maximum standardized uptake value (SUV(max)), liver SUV(max) and tumour/liver SUV(max) ratios were correlated with the findings of CT, shift MRI and final diagnosis (based on biopsy or clinical/radiological follow-up). A total of 109 adrenal masses were found: 49 were malignant and 60 were benign on final diagnosis. A tumour/liver SUV(max) ratio threshold of 1.0 was more accurate in differentiating the tumour type than tumour SUV(max) or visual interpretation alone. Diagnostic accuracy of CT and shift MRI (92 - 97%) was similar to that for FDG PET/CT (94 - 97%). In conclusion, FDG PET/CT accurately characterizes adrenal tumours, with excellent sensitivity and specificity. Use of 1.0 as the threshold for the tumour/liver SUV(max) ratio seems to be promising for distinguishing benign from malignant adrenal masses in cancer patients.

[CT and MR imaging of the facial nerve]. / Computer- und Magnetresonanztomographie des N. facialis.

Modern imaging techniques used for depicting the facial nerve include multi-slice spiral computed tomography (CT) and high-field magnetic resonance imaging (MRI). CT is the gold standard for imaging the osseous structures of the temporal bone. As a result of its excellent soft tissue contrast, MRI enables identification of the facial nerve itself. Due to high spatial resolution and the possibility to generate multiplanar reconstructions, both CT and MRI facilitate an exact evaluation of anatomical structures in all three spatial planes. The present article provides an overview of relevant anatomical structures, a thorough knowledge of which is the basic prerequisite to understanding pathologies and interpreting radiological findings correctly. Furthermore, basic techniques and strategies for imaging the facial nerve using CT and MRI are explained in general. The articles concludes with specific requirements for the radiological diagnosis of dysplasia, neoplasms and trauma, as well as vascular and inflammatory diseases.

Isotopic analysis of rare gases from stepwise heating of lunar fines and rocks.

Highlights of a first effort in sorting out rare gases in lunar material are solar wind rare gases in abundance; variable (20)Ne/(22)Ne but constant (21)Ne/ (22)Ne ratios in fractions of the trapped neon; cosmogenic rare gases similar to those found in meteorites, except for copious (131)Xe in one rock but not in another; at Tranquillity Base a rock 4.1 x 10(9) years old which reached the surface 35 to 65 million years ago, amid soil whose particles have typically been within a meter of the surface for 10(9) years or more.

Diffusion-weighted imaging (DWI) in MR mammography (MRM): clinical comparison of echo planar imaging (EPI) and half-Fourier single-shot turbo spin echo (HASTE) diffusion techniques.

Diffusion-weighted imaging (DWI) techniques have shown potential to differentiate between benign and malignant neoplasms. However, the diagnostic significance of using DWI under routine conditions remains unclear. This study investigated the use of echo planar imaging (EPI) and half-Fourier acquired single-shot turbo spin echo (HASTE)-DWI with respect to the three parameters: lesion visibility, apparent diffusion coefficient (ADC) measurements, and size estimation. Following MRM (1.5 T), EPI- and HASTE-DWI were applied in 65 patients. Lesion visibility on DWI was compared with lesion visibility on subtracted contrast-enhanced T1w images (CE-T1w). Statistical tests were applied to diameter, visibility, and ADC value measurements. Seventy-four lesions were identified. ADC value measurements did not differ significantly between the two DWI sequences. The sensitivity and specificity of routine diagnostics (97.4% and 85.7%) were superior to EPI-DWI (87.2% and 82.9%) and HASTE-DWI (76.9% and 88.6%). Selecting only nonmass lesions, DWI did not prove to be of diagnostic value. Lesion demarcation by DWI was significantly lower compared with that by CE-T1w, with EPI-DWI showing the better performance (p < 0.001). No significant differences were found for size measurements between CE-T1w and DWI. Although clearly inferior compared with CE-T1w imaging, both DWI techniques are applicable for lesion assessment and size measurements.

First Report of Diplodia Cane Dieback of Grapevine in Bolivia.

Grape (Vitis vinifera L.) is an important commercial crop in the temperate regions of Bolivia where it has been grown for hundreds of years. In October of 2001, diseased canes of grape (cv. Muscat of Alexandria) were collected in a vineyard in Yotala, Department of Chuquisaca in southern Bolivia. In this planting of more than 1,000 plants, more than 75% were exhibiting cane dieback symptoms and many were dead or dying. No disease was observed on grape berries. Symptoms of the disease were similar to those reported for Diplodia cane dieback (1). Cankers ranging from 2 to 10 cm long and 0.5 to 3 cm wide were observed. When diseased canes were placed in a moist chamber, conidia oozed from pycnidia in black cirri. Immature conidia were hyaline and one-celled, but mature conidia were dark brown (20 to 30 × 10 to 15 µm) with one median septum and longitudinal striations. The pathogen was tentatively identified as Lasiodiplodia theobromae (Pat.) Griffon & Maubl. (synonyms Diplodia natalensis Pole-Evans and Botryodiplodia theobromae Pat.), teleomorph Botryosphaeria rhodina (Cooke) Arx) (2). Fungi were isolated from cankers on diseased canes by surface disinfestation in 0.25% NaOCl for 5 min and placing small pieces of tissue on 2% water agar or potato dextrose agar (PDA). L. theobromae was isolated from these tissues. Koch's postulates were fulfilled by inoculating grape berries and canes with the pathogen. Five grape berries were surface disinfested and inoculated by wounding with a sterile scalpel and inserting a piece of fungal mycelium on PDA in the wounded sites. The same number of control berries was similarly treated with sterile PDA. Inoculated and control berries were placed in plastic, moist chambers in the laboratory at ambient temperature (15 to 28°C) in the dark. Five canes on two potted plants were inoculated with the same isolate of the pathogen in a similar manner as the berries. The inoculated and control sites on canes were wrapped with masking tape. Plants were placed in a moist chamber for 5 days. After 8 days, inoculated berries were rotting and the inoculated sites were covered with grayish mycelium. Within 12 days, cankers as much as 3 cm long developed on the inoculated canes, and in some lesions, black pycnidia were observed. No lesions developed in the wounded control canes. The pathogen was reisolated from inoculated berries and canes, but not from control berries or canes. The teleomorph was not observed on any naturally infected canes or on those inoculated with the anamorph. The pathogen was identified as L. theobromae based on symptoms (1), cultural and morphological characteristics (2), and pathogenicity tests. The disease poses a potential threat to the cultivation of grapevine in southern Bolivia. To our knowledge, this is the first report of Diplodia cane dieback of grapevine in Bolivia. References: R. C. Pearson and A. C. Goheen. Compendium of Grape Diseases. The American Phytopathological Society, St. Paul, MN, 1988. (2). E. Punithalingam. No. 519 in: Descriptions of Pathogenic Fungi and Bacteria. CMI, Kew, Surrey, England, 1976.

Kinetic Monte Carlo Study of the Role of the Energetic Disorder on the Open-Circuit Voltage in Polymer/Fullerene Solar Cells.

One major factor limiting the efficiency in organic solar cells (OSCs) is the low open-circuit voltage (Voc). Existing theoretical studies link the Voc with the charge transfer (CT) state and nonradiative recombination. However, also morphology and energetic disorder can have a strong impact on the Voc within realistic bulk-heterojunction OSCs. In this work, we present a kinetic Monte Carlo study on the role of the energetic disorder on the maximum Voc. We compute the quasi-Fermi level splitting for different energetic disorder and analyze the impact of the energetic disorder at the donor-acceptor interface as well as correlations in the site energies on the Voc. Our results show that the interface strongly controls the maximum Voc. For a higher interface disorder, charge densities and nongeminate recombination increase and the Voc is reduced. Furthermore, the correlated morphologies show an increase in the maximum Voc and a reduced impact of the energetic disorder.

Future innovations in anti-platelet therapies.

Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti-platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet-specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti-platelet agents. In this review, the mechanisms of platelet regulation and current anti-platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti-platelet drug development are discussed.

1.3 microm quantum dot laser in coupled-cavity-injection-grating design with bandwidth of 20 GHz under direct modulation.

Using a multi section laser in coupled cavity injection grating design based on 1.3 microm InGaAs/GaAs quantum dot (QD) active region we were able to enhance the 3 dB modulation bandwidth well beyond the inherent material modulation bandwidth. The material bandwidth was determined by measurements on distributed feedback (DFB) devices to approximately 8 GHz. The special multisectional design allows interaction between the lasing mode and a second mode used as catalyst and enables a high resonance frequency of the device. Based on active QD material this approach allowed us to reach a cut off frequency of 20 GHz in the small signal response of the device.

Effects of long-term immobilisation on cortical bone mass after traumatic amputation of the phalanges estimated by digital X-ray radiogrammetry.

UNLABELLED: Osteopenia of the cortical and trabecular bone partition is a common finding after immobilisation. Digital X-ray radiogrammetry (DXR) seems to quantify cortical demineralisation caused by circular saw amputation already few days after accident. INTRODUCTION: The study analyses the extent of demineralisation caused by immobilisation in patients with digital amputation after a circular saw injury, and elucidates the period of time which discloses a significant deprivation of bone mineral density estimated at the metacarpalia II-IV using DXR. METHODS: Twenty-eight patients with digital amputations underwent measurements of bone mineral density, cortical thickness, bone width and metacarpal index using DXR-technology in a follow-up up to 902 days. RESULTS: The data showed a significant decline of bone mineral density (-10.47%), the metacarpal index (-4.38%), the bone width (-12.06%) and the cortical thickness (-7.04%) after trauma-related amputation. The cortical demineralisation of the metacarpals could already be revealed in two patients after the second day, according to the amputation of phalanges (-3.65%). CONCLUSIONS: The inhibition of the periosteal bone formation detected by DXR-technique seems to be a specific finding caused by amputation, which thus differs from normal age-related (i.e., endosteal) bone loss and from demineralisation following acute immobilisation (i.e., trabecular osteopenia).

The mechanisms of refilling of xylem conduits and bleeding of tall birch during spring.

Seasonal variations in osmolality and components of xylem sap in tall birch trees were determined using several techniques. Xylem sap was extracted from branch and trunk sections of 58 trees using the very rapid gas bubble-based jet-discharge method. The 5-cm long wood pieces were taken at short intervals over the entire tree height. The data show that large biphasic osmolality gradients temporarily exist within the conducting xylem conduits during leaf emergence (up to 272 mosmol x kg(-1) at the apex). These gradients (arising mainly from glucose and fructose) were clearly held within the xylem conduit as demonstrated by (1)H NMR imaging of intact twigs. Refilling experiments with benzene, sucrose infusion, electron and light microscopy, as well as (1)H NMR chemical shift microimaging provided evidence that the xylem of birch represents a compartment confined by solute-reflecting barriers (radial: lipid linings/lipid bodies; axial: presumably air-filled spaces). These features allow transformation of osmolality gradients into osmotic pressure gradients. Refilling of the xylem occurs by a dual mechanism: from the base (by root pressure) and from the top (by hydrostatic pressure generated by xylem-bound osmotic pressure). The generation of osmotic pressure gradients was accompanied by bleeding. Bleeding could be observed at a height of up to 21 m. Bleeding rates measured at a given height decreased exponentially with time. Evidence is presented that the driving force for bleeding is the weight of the static water columns above the bleeding point. The pressure exerted by the water columns and the bleeding volume depend on the water-filling status of (communicating) vessels.

[Quantitation of glutamate in the brain by using MR proton spectroscopy at 1.5 T and 3 T]. / Quantitative Bestimmung von Glutamat im Hirn mithilfe der MR-Protonenspektroskopie bei 1,5 T und 3 T.

PURPOSE: The influence of different magnetic field strengths on the quantification of glutamate was experimentally investigated by means of IN VITRO and IN VIVO (1)H-MR spectroscopic measurements at 1.5 T and 3 T. MATERIALS AND METHODS: In vitro (1)H-MR measurements of aqueous solutions of NAA, glutamate, glutamine and GABA were performed on two clinical MR scanners at 1.5 T and 3 T using a single voxel PRESS sequence (TR/TE = 10 000 / 30 ms). IN VITRO brain measurements were also performed at both field strengths using a PRESS 2D- (1)H-CSI-sequence (TR/TE = 5000 / 30 ms) in 6 volunteers. Spectra at 1.5 T and 3 T were compared with respect to the overlap of the single compound spectra and the deviations between estimated and nominally adjusted concentrations. In vivo spectra at both field strengths were compared with respect to SNR (Glu), line width and Cramer-Rao values of the estimated glutamate intensities by using the LCModel. For the thalamus, insular and parietal cortex mean Glu/tCr ratios were estimated and compared between 1.5 T and 3 T as well as with corresponding values in the literature. RESULTS: In general, an improved separation of signal maxima was observed in the IN VITRO spectra at 3 T. Except for GABA, all IN VITRO concentrations estimated at 3 T revealed lower deviations from their adjusted nominal concentration compared to 1.5 T: NAA (1.5 T: -5.5 %, 3 T: 0.7 %), glutamate (1.5 T: -18.1 %, 3 T: 12.3 %), glutamine (1.5 T: 44.8 %, 3 T: 9.2 %), GABA (1.5 T: - 24.8 %, 3 T: 33.8 %). The SNR of IN VIVO spectra at 3 T was nearly doubled compared to 1.5 T. The mean number of voxels with %SD (Glu)< 20 was distinctly lower at 1.5 T (53 %) than at 3 T (80 %). Estimated Glu/tCr ratios for thalamus, insular and parietal cortex lay in the upper range of the literature values. CONCLUSION: The results indicate that the advantageous distribution of signal maxima at 3 T allows an improved separation of the individual spectra. Both the higher initial magnetization at 3 T and the improved sensitivity of the phased array matrix coil used in the 3 T study result in an increased SNR, which leads to better reliability of the individual detection as well as a more accurate quantification of glutamate.

[MRI screening before stem cell transplantation--necessary?]. / MRT-Untersuchung des Neurokraniums vor Stammzelltransplantation--notwendig oder überflüssig?

PURPOSE: In the context of stem cell transplantation (SCT), we often observe neurological complications as a consequence of immune system suppression, conditioning therapy or prophylaxis and treatment of graft-versus-host disease. Furthermore, cerebral lesions in existence prior to transplantation can be found. The aim of this study was to evaluate the benefit of cerebral magnetic resonance imaging (MRI) prior to stem cell transplantation. PATIENTS AND METHOD: Cerebral MR examinations of 116 children and adolescents were performed before SCT. Patients ranged in age from 1.1 to 21.4 years (mean 12.6 years). All MR images were obtained by a 1.5 T system. The predefined short protocol included an axial T 1-weighted SE sequence and a coronary T 2-weighted TSE sequence. We evaluated existing cerebral lesions, the diameter of the ventricular system, and the paranasal sinuses. In the case of pathological findings, the short examination protocol was expanded. RESULTS: In 5 of 116 children (4.3 %) we observed prior to SCT findings requiring immediate treatment although the patients did not show any clinical symptoms (1 x aspergilloma, 1 x hemorrhage of vascular anomaly). An increased risk of bleeding caused by cavernoma or another vascular anomaly without hemorrhage also had to be taken into account. 32 of 116 patients (37.1 %) showed atrophic lesions. In 42 children (36.2 %), we observed affections of the paranasal sinuses. CONCLUSION: The imaging findings requiring immediate treatment even though the children did not show any clinical signs, justify cerebral MR examinations prior to stem cell transplantation.

First Report of Ascochyta Blight Outbreak of Pea Caused by Ascochyta pisi in Spain.

Characteristic Ascochyta blight lesions were observed on leaves and stems of pea (Pisum sativum L.) 'Dove' grown at two sites in the province of Burgos (northern Spain) during May and June of 2005 and 2006. Mean disease severity of affected tissue reached 47% in 2005 and 72% in 2006. Dark brown, circular, necrotic lesions were sometimes covered with pycnidia. Fungal isolations were made from small pieces of infected tissue by surface disinfecting in 1% NaOCl for 1 min and then washing in deionized, sterile water for 2 min. Tissue pieces were placed on potato dextrose agar (PDA) for 7 days at 20 to 24°C under fluorescents lights with a 12-h photoperiod to induce sporulation. Single-spore isolations were made by streaking conidia from PDA cultures on 2% water agar and picking germinated conidia after 18 h. Fungal colonies grown on PDA and conidia from these cultures were similar to that of Ascochyta pisi Lib., and no chlamydospores or pseudothecia were observed, eliminating the possibility that the isolated fungi were A. pinodes or A. pinodella (3), the other fungi associated with the "Ascochyta complex" of pea. Conidial suspensions (5 × 105 conidia/ml) of two single-spore isolates (Spain-47 and Spain-48) were spray inoculated to runoff on 3-week-old plants of bean (Phaseolus vulgaris L. 'Contender'), chickpea (Cicer arietinum L. 'Blanco lechoso'), lentil (Lens culinaris Medik. 'Pardinar'), pea ('Lincoln'), and faba bean (Vicia faba L. 'Alameda') with 10 replicate plants per isolate. Plants were incubated in a growth chamber at 20 to 24°C and 100% relative humidity (RH) for 48 h and then incubated at the same temperature and 50 to 80% RH for 3 weeks. Characteristic Ascochyta blight lesions were apparent 7 days after inoculation on leaves and stems of pea. No disease symptoms were observed on the other inoculated plants. DNA was extracted from both isolates (Spain-47 and Spain-48) and 610 bp of the glyceraldehyde-3-phosphate-dehydrogenase gene (G3PD) was amplified with gpd-1 and gpd-2 primers (2). Amplicons were direct sequenced on both strands and consensus sequences were aligned. Spain-47 and Spain-48 had identical sequences. A BLAST search of the NCBI nucleotide database with the consensus sequence revealed A. pisi G3PD Accession No. DQ383963 (isolate ATCC 201617, Bulgaria) as the closest match in the database with 100% sequence similarity. These results, coupled with the morphological identification and inoculation results, confirm the identity of the fungus as A. pisi. Although infections by A. pinodes or by unidentified Ascochyta spp. are well known in pea crops in Spain (1), to our knowledge, this is the first report of an outbreak of Ascochyta blight of pea caused by A. pisi under field conditions in Spain. References: (1) M. F. Andrés et al. Patógenos de Plantas Descritos en España. MEC, Madrid, 1998. (2) M. L. Berbee et al. Mycologia 91:964, 1999. (3) E. Punithalingam and P. Holliday. No 334 in: Descriptions of Pathogenic Fungi and Bacteria. CMI, Kew, Surrey, UK, 1972.

The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and hemostasis.

Essentials Heat shock protein 47 (HSP47), a collagen specific chaperone is present on the platelet surface. Collagen mediated platelet function was reduced following blockade or deletion of HSP47. GPVI receptor regulated signalling was reduced in HSP47 deficient platelets. Platelet HSP47 tethers to exposed collagen thus modulating thrombosis and hemostasis. SUMMARY: Objective Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering hemostasis and thrombosis, in this study we sought to characterize the role of HSP47 in these cells. Methods and Results The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP-XL), but responses to thrombin were unaltered. In the absence of functional HSP47, the interaction of collagen with platelets was reduced, and this was associated with reduced GPVI-collagen binding, signalling and platelet activation. Thrombus formation on collagen, under arterial flow conditions, was also decreased following the inhibition or deletion of HSP47, in the presence or absence of eptifibatide, consistent with a role for HSP47 in enhancing platelet adhesion to collagen. Platelet adhesion under flow to von Willebrand factor was unaltered following HSP47 inhibition. Laser-induced thrombosis in cremaster muscle arterioles was reduced and bleeding time was prolonged in HSP47-deficient mice or following inhibition of HSP47. Conclusions Our study demonstrates the presence of HSP47 on the platelet surface, where it interacts with collagen, stabilizes platelet adhesion and increases collagen-mediated signalling and therefore thrombus formation and hemostasis.

Inhibitor of apoptosis proteins physically interact with and block apoptosis induced by Drosophila proteins HID and GRIM.

Reaper (RPR), HID, and GRIM activate apoptosis in cells programmed to die during Drosophila development. We have previously shown that transient overexpression of RPR in the lepidopteran SF-21 cell line induces apoptosis and that members of the inhibitor of apoptosis (IAP) family of antiapoptotic proteins can inhibit RPR-induced apoptosis and physically interact with RPR through their BIR motifs (D. Vucic, W. J. Kaiser, A. J. Harvey, and L. K. Miller, Proc. Natl. Acad. Sci. USA 94:10183-10188, 1997). In this study, we found that transient overexpression of HID and GRIM also induced apoptosis in the SF-21 cell line. Baculovirus and Drosophila IAPs blocked HID- and GRIM-induced apoptosis and also physically interacted with them through the BIR motifs of the IAPs. The region of sequence similarity shared by RPR, HID, and GRIM, the N-terminal 14 amino acids of each protein, was required for the induction of apoptosis by HID and its binding to IAPs. When stably overexpressed by fusion to an unrelated, nonapoptotic polypeptide, the N-terminal 37 amino acids of HID and GRIM were sufficient to induce apoptosis and confer IAP binding activity. However, GRIM was more complex than HID since the C-terminal 124 amino acids of GRIM retained apoptosis-inducing and IAP binding activity, suggesting the presence of two independent apoptotic motifs within GRIM. Coexpression of IAPs with HID stabilized HID levels and resulted in the accumulation of HID in punctate perinuclear locations which coincided with IAP localization. The physical interaction of IAPs with RPR, HID, and GRIM provides a common molecular mechanism for IAP inhibition of these Drosophila proapoptotic proteins.

Impact on adenosine stress cardiac magnetic resonance for recanalisation and follow up of chronic total coronary occlusions.

OBJECTIVE: To evaluate the impact on cardiac magnetic resonance imaging (CMRI) with adenosine stress and delayed enhancement for indication and follow up after interventional recanalisation of chronic total coronary occlusions (CTOs). MATERIAL AND METHODS: Twenty consecutive patients (15 males; 5 females; mean age 65 years) with CTO verified by cardiac catheterisation referred to CMRI. Sixteen of them got CMRI before and after coronary recanalisation. Wall motion abnormalities (WMAs), first pass perfusion with adenosine and viability were assessed using a 1.5 T MR scanner (Sonata; Siemens). CMRI results were compared with clinical classifications, the results of cardiac catheterisation and follow up angiography. RESULTS: Sixteen patients had a successful recanalisation, 15 of the occluded coronary artery and one of collateral donor artery stenosis. After recanalisation all stress-induced progressive or new wall motion abnormalities (WMAs) of the corresponding segments and in the collateral donor territory (5 patients) and all adenosine induced perfusion defects (PD) or delay (12 patients) were regredient. 13/16 patients showed no transmural and one patient transmural delayed enhancement (DE) indicating myocardial scar. In 10/16 patients CSS grading of angina improved after recanalisation. CONCLUSION: After successful recanalisation of CTOs, patients with preinterventional stress-induced PDs and WMAs in viable myocardium did not display any signs of stress-induced ischemia postinterventionally. A comprehensive CMRI approach, including assessment of rest and stress WMAs, first pass perfusion and myocardial viability represents an important tool for the pre-interventional decision to recanalise CTOs and follow up.

Prediction of periodontal disease from multiple self-reported items in a German practice-based sample.

BACKGROUND: Ascertainment of periodontal disease using self-reported measures would be useful for large epidemiologic studies. This study evaluates whether a combination of self-reported items with established risk factors in a predictive model can assess periodontal disease accurately. METHODS: Responses of 246 subjects to a detailed questionnaire were compared to their periodontal disease history as assessed from radiographs. Multiple regression modeling was used to construct predictive models using self-reported items and established risk factors. RESULTS: Depending on the definition of gold-standard periodontal disease, two or three self-reported items were selected for the predictive models, in addition to age, gender, and smoking. Self-reported tooth mobility was associated strongly with periodontal disease independent of other risk factors and was selected in all models. For dichotomous definitions of periodontal disease, discrimination of predictive logistic regression models was good with areas under the receiver operating characteristic curve >0.80. Assessment of periodontal disease history based on extreme quantiles of model-predicted values yielded high sensitivity and specificity. CONCLUSION: The combination of several self-reported items may be useful for ascertainment of periodontal disease in epidemiologic studies.