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1.
Eur Radiol ; 29(11): 5742-5751, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30993437

ABSTRACT

OBJECTIVES: To evaluate the lesion-to-liver visual signal intensity ratio (SIR) before and at the hepatobiliary phase MRI (HBP-MRI) after gadobenate dimeglumine (Gd-BOPTA) injection, using several T1-weighted images (T1-WI), for the characterization of benign hepatocellular lesions. METHODS: Patients with histologically proven focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), who underwent Gd-BOPTA-enhanced HBP-MRI from 2009 to 2017, were retrospectively identified. The lesion-to-liver SIR was visually assessed by two radiologists on HBP (post-HBP analysis) and compared with that of unenhanced sequences (pre/post-HBP analysis) on T1-WI in-phase (T1-IP), out-of-phase (T1-OP), and fat suppression (T1-FS). Lesions were classified as hyper-, iso-, or hypointense on post-HBP, and as decreasing, stable, or increasing SIR on pre/post-HBP analyses. The performance of the different T1-WI sequences for the diagnostic of FNH was evaluated on post-HBP analysis. RESULTS: Twenty-nine FNHs and 33 HCAs were analyzed. On post-HBP analysis, FNHs appeared hyper-/isointense in 89.7% of all T1-WI. HCAs appeared hypointense in 93.9%, 63.6%, and 69.7% of T1-IP, T1-OP, and T1-FS, respectively. FNHs exhibited an increasing SIR in 55.2-58.6%, a stable SIR in 44.8-58.6%, and a decreasing SIR in 0%, whereas HCAs exhibited a decreasing SIR in 66.7-93.9%, a stable SIR in 6.1-33.3%, and an increasing SIR in 0% (p < 0.0001). The specificity of T1-IP was significantly higher than that of T1-OP (p = 0.015) and T1-FS (p = 0.042). CONCLUSION: T1-IP is the most reliable sequence due to misleading tumor/liver signal ratio in the case of fatty liver when using T1-FS or T1-OP. The pre/post-HBP lesion-to-liver SIR is accurate to classify benign hepatocellular lesions and contributes to avoid biopsy. KEY POINTS: •The T1-weighted images in-phase should be systematically included in the HBP-MRI protocol, as it is the most reliable sequence especially in the case of fatty liver. •The comparison between lesion-to-liver signal intensity ratios on unenhanced and at the hepatobiliary phase sequences is useful to classify benign hepatocellular lesions in three categories without misclassification: FNH (increasing signal intensity ratio), HCA (decreasing signal intensity ration), and indeterminate lesions (stable signal intensity ratio).


Subject(s)
Adenoma, Liver Cell/pathology , Carcinoma, Hepatocellular/pathology , Focal Nodular Hyperplasia/pathology , Liver Neoplasms/pathology , Adult , Biopsy , Contrast Media , Fatty Liver/pathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Meglumine/analogs & derivatives , Middle Aged , Organometallic Compounds , Retrospective Studies , Sensitivity and Specificity , Young Adult
2.
Acta Radiol ; 56(12): 1527-33, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25512947

ABSTRACT

BACKGROUND: Many candidates for kidney transplantation need to undergo vessel examination before the transplantation procedure. PURPOSE: To identify the optimal preoperative modality for the examination of vessel status without the use of contrast agents in kidney transplant candidates. MATERIAL AND METHODS: Fifty-three consecutive patients were examined and 31 patients were transplanted. Ultrasonography (US), non-contrast-enhanced computed tomography (NCCT), and non-contrast-enhanced magnetic resonance angiography (NCMRA) were compared using inspection during kidney transplantation (TX) as a reference standard. The sensitivity and specificity to severe arteriosclerotic changes and the accuracy were calculated. Kappa statistics were used to assess the agreement between TX and the different examination modalities, and McNemar's test was used to test for significant differences. RESULTS: US had higher sensitivity (1.0) and better agreement with observations from surgery (k = 0.89) than both NCCT (sensitivity = 0.60; k = 0.72) and NCMRA (sensitivity = 0.20; k = 0.30). No significant difference was found between TX and US (P = 0.3173) or TX and NCCT (P = 0.1573), but there was a significant difference between TX and NCMRA (P = 0.0455). US was inconclusive in 20% of cases, and the internal iliac artery could not be visualized in 69% of cases. CONCLUSION: Either US or NCCT can be used as the preferred preoperative imaging modality to examine vessel status before kidney transplantation, but a combination of the two is preferable. NCMRA should not be used as the sole imaging modality for preoperative imaging before kidney transplantation because of its low sensitivity in detecting severe arteriosclerotic disease without the presence of stenosis.


Subject(s)
Kidney Transplantation , Kidney/diagnostic imaging , Magnetic Resonance Angiography , Preoperative Care/methods , Tomography, X-Ray Computed , Adult , Aged , Female , Humans , Kidney/pathology , Male , Middle Aged , Sensitivity and Specificity , Ultrasonography
3.
Eur Radiol ; 23(6): 1510-8, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23300043

ABSTRACT

OBJECTIVE: To perform preliminary tests in vitro and with healthy volunteers to determine the 3-T MRI compatibility of a cochlear implant with a non-removable magnet. METHODS: In the in vitro phase, we tested six implants for temperature changes and internal malfunctioning. We measured the demagnetisation of 65 internal magnets with different tilt angles between the implant's magnetic field (bi) and the main magnetic field (b0). In the in vivo phase, we tested 28 operational implants attached to the scalps of volunteers with the head in three different positions. RESULTS: The study did not find significant temperature changes or electronic malfunction in the implants tested in vitro. We found considerable demagnetisation of the cochlear implant magnets in the in vitro and in vivo testing influenced by the position of the magnet in the main magnetic field. We found that if the bi/b0 angle is <90°, there is no demagnetisation; if the bi/b0 angle is >90°, there is demagnetisation in almost 60 % of the cases. When the angle is around 90°, the risk of demagnetisation is low (6.6 %). CONCLUSION: The preliminary results on cochlear implants with non-removable magnets indicate the need to maintain the contraindication of passage through 3-T MRI. KEY POINTS: • Magnetic resonance imaging can affect cochlear implants and vice versa. • Demagnetisation of cochlear implant correlates with the angle between bi and b0. • The position of the head in the MRI influences the demagnetisation. • Three-Tesla MRI for cochlear implants is still contraindicated. • However some future solutions are discussed.


Subject(s)
Cochlear Implantation/instrumentation , Cochlear Implants , Magnetic Resonance Imaging/methods , Cochlear Implantation/methods , Electronics , Equipment Design , Humans , Magnets , Materials Testing , Prosthesis Design , Temperature
4.
Transpl Int ; 25(9): 1002-12, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22775333

ABSTRACT

Delayed graft function (DGF) complicates approximately 25% of kidney allografts donated after brain death (DBD). Remote ischaemic conditioning (rIC) involves brief, repetitive, ischaemia in a distant tissue in connection with ischaemia/reperfusion in the target organ. rIC has been shown to induce systemic protection against ischaemic injuries. Using a porcine kidney transplantation model with donor (63 kg) recipient (15 kg) size mismatch, we investigated the effects of recipient rIC on early renal plasma perfusion and GFR. Brain death was induced in donor pigs (n = 8) and kidneys were removed and kept in cold storage until transplantation. Nephrectomized recipient pigs were randomized to rIC (n = 8) or non-rIC (n = 8) with one kidney from the same donor in each group. rIC consisted of 4 × 5 min clamping of the abdominal aorta. GFR was significantly higher in the rIC group compared with non-rIC (7.2 ml/min vs. 3.4 ml/min; ΔGFR = 3.7 ml/min, 95%-CI: 0.3-7.2 ml/min, P = 0.038). Renal plasma perfusion in both cortex and medulla measured by dynamic contrast-enhanced magnetic resonance imaging (MRI) was significantly higher over time in the rIC group compared with non-rIC. This experimental study demonstrated a positive effect of rIC on early graft perfusion and function in a large animal transplantation model.


Subject(s)
Glomerular Filtration Rate , Ischemia/pathology , Kidney Diseases/therapy , Kidney Transplantation/methods , Kidney/pathology , Animals , Biomarkers , Blood Pressure , Female , Heme Oxygenase-1/metabolism , Magnetic Resonance Imaging/methods , Nephrectomy/methods , Perfusion , Swine , Transplantation Conditioning
5.
Sci Adv ; 7(12)2021 03.
Article in English | MEDLINE | ID: mdl-33731353

ABSTRACT

For the two proteins myoglobin and fluoroacetate dehalogenase, we present a systematic comparison of crystallographic diffraction data collected by serial femtosecond (SFX) and serial synchrotron crystallography (SSX). To maximize comparability, we used the same batch of micron-sized crystals, the same sample delivery device, and the same data analysis software. Overall figures of merit indicate that the data of both radiation sources are of equivalent quality. For both proteins, reasonable data statistics can be obtained with approximately 5000 room-temperature diffraction images irrespective of the radiation source. The direct comparability of SSX and SFX data indicates that the quality of diffraction data obtained from these samples is linked to the properties of the crystals rather than to the radiation source. Therefore, for other systems with similar properties, time-resolved experiments can be conducted at the radiation source that best matches the desired time resolution.


Subject(s)
Proteins , Synchrotrons , Crystallography, X-Ray
6.
Eur Radiol ; 20(11): 2628-36, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20862477

ABSTRACT

OBJECTIVES: The aim of this longitudinal study is to describe the different intralabyrinthine lesions yielding high signal intensity on T1-weighted (T1W) images after intravenous gadolinium and then to analyze the follow-up of these patients. METHODS: Thirty-seven patients were included and followed clinically and radiologically. A precise analysis of MR labyrinthine signals allowed exact depiction of the different lesions. Special interest is focused on the intralabyrinthine fluid signal on 3D high-resolution T2W images. RESULTS: The enhanced T1W labyrinthine hyperintensities correspond to two different categories: intralabyrinthine enhancement (15 intralabyrinthine schwannomas, 13 labyrinthitis, 1 inflammatory granuloma) and spontaneous T1W hyperintensities (8 intralabyrinthine hemorrhages). Hemorrhagic lesions show a substantial decrease of the intralabyrinthine fluid signal on the 3D HRT2 that evolves to ossification. In labyrinthitis, the importance of the initial labyrinthine fluid signal decrease on the 3D HRT2 is well correlated with the hearing prognosis. CONCLUSION: A meticulous analysis of inner ear lesions allows various intralabyrinthine lesions, in particular schwannomas, to be differentiated from labyrinthitis. T1W imaging without gadolinium is essential for the correct diagnosis of rapidly evolving hearing loss. In labyrinthitis and intralabyrinthine hemorrhage, 3D HRT2 brings an interesting prognostic factor for the chance of hearing recovery.


Subject(s)
Contrast Media , Ear Neoplasms/diagnosis , Gadolinium , Labyrinth Diseases/diagnosis , Labyrinthitis/diagnosis , Magnetic Resonance Imaging , Neurilemmoma/diagnosis , Adolescent , Adult , Aged , Diagnosis, Differential , Ear, Inner/pathology , Female , Humans , Male , Middle Aged , Prognosis , Young Adult
7.
J Visc Surg ; 157(6): 469-474, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32088182

ABSTRACT

INTRODUCTION: Serious caustic burns of the stomach that present with no clinico-biological severity criteria (CBSC) can be treated conservatively. However, even if there are no CBSC at admission, 20% of patients still require delayed emergency surgery for peritonitis due to gastric perforation thus showing the limitations of this strategy in the diagnosis of irreversible gastric necrosis lesions. The aim of this study was to identify reliable computed tomography (CT) signs of irreversible gastric necrosis in patients with stage 3 endoscopic lesions. PATIENTS AND METHODS: In a prospective study from March 2014 to January 2017, thoraco-abdomino-pelvic CT scan was performed in 30 consecutive patients with stage 3 endoscopic gastric lesions. The CT results were concealed from the clinicians and compared to CBSC results. RESULTS: Twenty patients were treated conservatively and ten patients were operated on. Seventy percent of the patients underwent urgent delayed surgery for symptoms that developed late but before alterations in the CBSC. The CT scan showed a perfusion defect (PD) of gastric mucosal enhancement in all patients operated on for gastrointestinal distress, and could have provided an early diagnosis of irreversible gastric necrosis. CONCLUSION: CT was a more effective diagnostic tool for the diagnosis of irreversible gastric necrosis following caustic ingestion than a strategy based on digestive endoscopy and the use of CBSC. CT could eventually replace gastrointestinal endoscopy in the emergency evaluation of gastroesophageal caustic burns.


Subject(s)
Burns, Chemical/etiology , Burns, Chemical/surgery , Caustics/poisoning , Gastritis/chemically induced , Gastritis/surgery , Tomography, X-Ray Computed , Algorithms , Burns, Chemical/diagnostic imaging , Female , Gastritis/diagnostic imaging , Gastroscopy , Humans , Male , Middle Aged , Necrosis , Prospective Studies , Suicide, Attempted/psychology
8.
Abdom Radiol (NY) ; 45(11): 3589-3607, 2020 11.
Article in English | MEDLINE | ID: mdl-32296900

ABSTRACT

PURPOSE: The aim of the study is to describe the imaging features, complications and differential diagnoses of abdominal cystic lymphangiomas (ACLs). RESULTS: ACLs are benign lymphatic malformations that mainly arise in the subperitoneal space and the retroperitoneum. The typical presentation of an ACL is a multilocular lesion with homogenous serous content, presenting a thin wall and septa, usually free from adjacent organ compression. Atypical findings, including fat or hemorrhagic content, septal calcifications and unilocular presentation, are not uncommon. Rarely, ACLs can be revealed by acute complications, such as infection, hemorrhage, intussusception, complications with a twisting mechanism (including torsion around its own pedicle) or spontaneous rupture, which can be diagnosed by imaging. Ultrasonography and CT are the most useful modalities in emergency situations. MRI performs best in the noninvasive characterization of cystic lesions. ACLs should be differentiated from normal anatomic structures (e.g., cisterna chyli) or pitfalls (e.g., ascites, extrapancreatic necrosis, lymphocele) that can simulate ACLs. Among other primary peritoneal cystic lesions, benign cystic mesothelioma can be difficult to differentiate from ACL. Some neoplastic peritoneal lesions may have cystic components or content that looks like fluid on imaging (such as mucinous or myxoid content) and be misdiagnosed as ACL. Nodular or thick enhancement of the wall or septa should then be considered worrisome features and should not suggest ACL. ACLs mostly require a simple follow-up. If treatment is necessary, percutaneous sclerotherapy is a safe and effective alternative to surgery. CONCLUSION: Imaging, especially MRI, allows the noninvasive diagnosis of ACL and helps to exclude potential malignant differential diagnoses.


Subject(s)
Lymphangioma, Cystic , Retroperitoneal Neoplasms , Diagnosis, Differential , Humans , Lymphangioma, Cystic/diagnostic imaging , Ultrasonography
9.
Diagn Interv Imaging ; 101(12): 789-794, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32451309

ABSTRACT

PURPOSE: The purpose of this study was to build and train a deep convolutional neural networks (CNN) algorithm to segment muscular body mass (MBM) to predict muscular surface from a two-dimensional axial computed tomography (CT) slice through L3 vertebra. MATERIALS AND METHODS: An ensemble of 15 deep learning models with a two-dimensional U-net architecture with a 4-level depth and 18 initial filters were trained to segment MBM. The muscular surface values were computed from the predicted masks and corrected with the algorithm's estimated bias. Resulting mask prediction and surface prediction were assessed using Dice similarity coefficient (DSC) and root mean squared error (RMSE) scores respectively using ground truth masks as standards of reference. RESULTS: A total of 1025 individual CT slices were used for training and validation and 500 additional axial CT slices were used for testing. The obtained mean DSC and RMSE on the test set were 0.97 and 3.7 cm2 respectively. CONCLUSION: Deep learning methods using convolutional neural networks algorithm enable a robust and automated extraction of CT derived MBM for sarcopenia assessment, which could be implemented in a clinical workflow.


Subject(s)
Abdominal Muscles , Deep Learning , Sarcopenia , Tomography, X-Ray Computed , Abdominal Muscles/diagnostic imaging , Algorithms , Humans , Neural Networks, Computer , Sarcopenia/diagnostic imaging
10.
Diagn Interv Imaging ; 101(12): 783-788, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32245723

ABSTRACT

PURPOSE: The second edition of the artificial intelligence (AI) data challenge was organized by the French Society of Radiology with the aim to: (i), work on relevant public health issues; (ii), build large, multicentre, high quality databases; and (iii), include three-dimensional (3D) information and prognostic questions. MATERIALS AND METHODS: Relevant clinical questions were proposed by French subspecialty colleges of radiology. Their feasibility was assessed by experts in the field of AI. A dedicated platform was set up for inclusion centers to safely upload their anonymized examinations in compliance with general data protection regulation. The quality of the database was checked by experts weekly with annotations performed by radiologists. Multidisciplinary teams competed between September 11th and October 13th 2019. RESULTS: Three questions were selected using different imaging and evaluation modalities, including: pulmonary nodule detection and classification from 3D computed tomography (CT), prediction of expanded disability status scale in multiple sclerosis using 3D magnetic resonance imaging (MRI) and segmentation of muscular surface for sarcopenia estimation from two-dimensional CT. A total of 4347 examinations were gathered of which only 6% were excluded. Three independent databases from 24 individual centers were created. A total of 143 participants were split into 20 multidisciplinary teams. CONCLUSION: Three data challenges with over 1200 general data protection regulation compliant CT or MRI examinations each were organized. Future challenges should be made with more complex situations combining histopathological or genetic information to resemble real life situations faced by radiologists in routine practice.


Subject(s)
Artificial Intelligence , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Humans , Radiologists
11.
J Radiol ; 90(3 Pt 2): 409-12, 2009 Mar.
Article in French | MEDLINE | ID: mdl-19421131

ABSTRACT

3-Phase contrast material enhanced CT provides great sensitivity for accurate localization of hyperfunctioning parathyroid glands. Density measurements can assist in differentiating adenomas from lymph nodes and normal thyroid tissue. The spontaneous attenuation of parathyroid adenomas is lower than 80 HU, whereas the density of normal thyroid tissue is above 80 HU. Forty five seconds after contrast injection, adenomas have a density>130 HU, whereas lymph nodes have a density<130 HU. Furthermore, between 45 and 70 seconds after injection, the attenuation of parathyroid adenomas decreases (>20UH) whereas the attenuation of lymph nodes increases.


Subject(s)
Adenoma/diagnostic imaging , Hyperparathyroidism, Primary/diagnostic imaging , Parathyroid Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Adenoma/diagnosis , Contrast Media , Diagnosis, Differential , Female , Humans , Hypercalcemia/etiology , Hyperparathyroidism, Primary/diagnosis , Lymph Nodes/diagnostic imaging , Magnetic Resonance Imaging , Middle Aged , Parathyroid Glands/diagnostic imaging , Parathyroid Neoplasms/diagnosis , Sensitivity and Specificity , Time Factors
12.
Trends Biochem Sci ; 26(5): 318-24, 2001 May.
Article in English | MEDLINE | ID: mdl-11343925

ABSTRACT

G-protein-coupled receptors (GPCRs) are involved in a vast variety of cellular signal transduction processes from visual, taste and odor perceptions to sensing the levels of many hormones and neurotransmitters. As a result of agonist-induced conformation changes, GPCRs become activated and catalyze nucleotide exchange within the G proteins, thus detecting and amplifying the signal. GPCRs share a common heptahelical transmembrane structure as well as many conserved key residues and regions. Rhodopsins are prototypical GPCRs that detect photons in retinal photoreceptor cells and trigger a phototransduction cascade that culminates in neuronal signaling. Biophysical and biochemical studies of rhodopsin activation, and the recent crystal structure determination of bovine rhodopsin, have provided new information that enables a more complete mechanism of vertebrate rhodopsin activation to be proposed. In many aspects, rhodopsin might provide a structural and functional template for other members of the GPCR family.


Subject(s)
Rhodopsin/chemistry , Rhodopsin/metabolism , Amino Acid Sequence , Animals , Cattle , Cytoplasm/metabolism , GTP-Binding Proteins/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Humans , Models, Chemical , Models, Molecular , Molecular Sequence Data , Photons , Protein Conformation , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/metabolism , Retinal Diseases/metabolism , Signal Transduction
13.
Abdom Radiol (NY) ; 44(5): 1734-1743, 2019 05.
Article in English | MEDLINE | ID: mdl-30758535

ABSTRACT

PURPOSE: To present radiological aspects of jejunoileal diverticulosis and its complications. RESULTS: Jejunoileal diverticulosis is a relatively rare and underestimated condition, which mostly affects the elderly. It is frequently asymptomatic but it can lead to significant complications requiring surgical treatment. Jejunoileal diverticulosis is far less common than colonic diverticulosis. Acquired small bowel diverticula are often numerous but the complication rate is low. Acute diverticulitis is the most frequent complication; its classic presentation involves the jejunum and is often non-severe. Diverticular hemorrhage is the second most common complication; CT scan examination is essential to determine the accurate topography of the pathological diverticula. Small bowel obstruction can occur through several mechanisms: adhesions, enterolith, and intussusception. Extra-intestinal gas without perforation and "pseudo-ischemic" appearance are non-pathological conditions that are important to diagnose in order to avoid surgery. CONCLUSION: Jejunoileal diverticulosis usually does not show any symptoms but can lead to diagnostic challenges requiring evaluation by CT. CT scan signs of these complications and some pitfalls must be known.


Subject(s)
Diverticular Diseases/complications , Diverticular Diseases/diagnostic imaging , Jejunal Diseases/complications , Jejunal Diseases/diagnostic imaging , Tomography, X-Ray Computed , Diagnosis, Differential , Humans
14.
Diabetes Metab ; 45(1): 67-75, 2019 01.
Article in English | MEDLINE | ID: mdl-30165155

ABSTRACT

AIM: The adipo-myokine irisin regulates energy expenditure and fat metabolism. LMNA-associated familial partial lipodystrophy (FPLD2) comprises insulin resistance, muscle hypertrophy and lipoatrophy. The aim of this study was to investigate whether irisin could be a biomarker of FPLD2. PATIENTS AND METHODS: This case control study included 19 FPLD2 subjects, 13 obese non-diabetic (OND) patients and 19 healthy controls (HC) of normal weight (median BMI: 26, 39 and 22 kg/m2, respectively). Serum irisin and leptin levels, body composition (DXA/MRI) and metabolic/inflammatory parameters were compared in these three groups. RESULTS: BMI and MRI intra-abdominal fat significantly differed among these three groups, whereas DXA total fat mass and leptin levels were higher in the OND group, but did not differ between HC and FPLD2. Lipodystrophy patients had higher intra-abdominal/total abdominal fat ratios than the other two groups. Irisin levels were higher in FPLD2 and OND patients than in HC (medians: 944, 934 and 804 ng/mL, respectively). However, irisin/leptin ratios and lean body mass percentages were strikingly higher, and lean mass indices lower, in FPLD2 and HC than in the OND (median irisin/leptin ratios: 137, 166 and 21, respectively). In the entire study group, irisin levels positively correlated with BMI, lean body mass and index, intra-abdominal/total abdominal fat ratio, triglyceride, cholesterol, insulin, glucose and HbA1c levels. Also, intra-abdominal/total abdominal fat ratio and lean body mass better differentiated the three groups only in female patients. CONCLUSION: Circulating irisin is similarly increased in FPLD2 and OND patients, who are characterized by higher lean body mass regardless of their clearly different fat mass. However, irisin/leptin ratios, strikingly higher in FPLD2 than in OND patients, could help to make the diagnosis and prompt genetic testing in clinically atypical cases.


Subject(s)
Fibronectins/blood , Lamin Type A/genetics , Lipodystrophy, Familial Partial/blood , Absorptiometry, Photon , Adult , Blood Glucose , Body Composition/physiology , Body Mass Index , Case-Control Studies , Female , Humans , Insulin/blood , Leptin/blood , Lipodystrophy, Familial Partial/diagnostic imaging , Lipodystrophy, Familial Partial/genetics , Magnetic Resonance Imaging , Male , Middle Aged , Obesity/blood , Obesity/diagnostic imaging , Triglycerides/blood , Young Adult
15.
Invest Ophthalmol Vis Sci ; 49(3): 1106-15, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18326738

ABSTRACT

PURPOSE: To describe and classify the morphologic changes in a naturally occurring dog model of early-onset cone-rod dystrophy (CRD) and to correlate these with earlier described clinical characteristics of the disease in dogs. METHODS: Purpose-bred Standard Wire-Haired Dachshunds (SWHDs) derived from a large pedigree of dogs with early-onset CRD were euthanatized at defined ages to characterize morphologic changes in the disease process. Specimens were examined by light microscopy, including morphometric studies, electron microscopy, and immunohistochemistry. Peanut agglutinin (PNA), protein kinase C (PKC), synaptophysin (Syn), rhodopsin (Rho)-63, glial fibrillary acidic protein (GFAP), and short-wavelength cone opsin (OS) were used for immunohistochemical characterization. RESULTS: The photopic cone-system-derived ERG amplitudes were already significantly reduced or nonrecordable in CRD-affected dogs at 5 weeks, the earliest age studied. The outer retina was morphologically most severely affected initially, with a subsequent degeneration of the inner retina. Cone degeneration was more pronounced than rod degeneration in young CRD-affected dogs. There was a marked phenotypic variation based on morphologic findings in the affected dogs. At the earliest time point studied (5-8 weeks) cone photoreceptor and glial cell abnormalities were observed, in accordance with earlier studies based on electrophysiological and clinical findings in which day blindness and abnormal cone ERGs were observed in young affected SWHD puppies. Preliminary genetic studies have indicated an autosomal recessive mode of inheritance for the defect. CONCLUSIONS: Through functional and structural characterization, early-onset cone abnormalities were found, consistent with a cone dysplasia at an age when rod structure was normal. Further studies are in progress to identify the gene(s) involved in this retinal disease process. The presently described natural animal model of primary cone dysplasia followed by rod degeneration may provide further insight into the human counterpart. Further studies are needed to ascertain an autosomal recessive mode of inheritance for CRD in the SWHD.


Subject(s)
Dog Diseases/physiopathology , Electroretinography/veterinary , Photoreceptor Cells, Vertebrate , Retina/physiopathology , Retina/ultrastructure , Retinal Degeneration/veterinary , Animals , Disease Models, Animal , Dog Diseases/metabolism , Dogs , Female , Fluorescent Antibody Technique, Indirect , Glial Fibrillary Acidic Protein/metabolism , Male , Microscopy, Electron , Pedigree , Phenotype , Photoreceptor Cells, Vertebrate/physiology , Photoreceptor Cells, Vertebrate/ultrastructure , Protein Kinase C/metabolism , Retina/metabolism , Retinal Degeneration/metabolism , Retinal Degeneration/physiopathology , Rhodopsin/metabolism , Rod Opsins/metabolism , Synaptophysin/metabolism
16.
Nat Biotechnol ; 17(11): 1105-8, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10545918

ABSTRACT

G protein-coupled receptors (GPCRs) constitute an abundant family of membrane receptors of high pharmacological interest. Cell-based assays are the predominant means of assessing GPCR activation, but are limited by their inherent complexity. Functional molecular assays that directly and specifically report G protein activation by receptors could offer substantial advantages. We present an approach to immobilize receptors stably and with defined orientation to substrates. By surface plasmon resonance (SPR), we were able to follow ligand binding, G protein activation, and receptor deactivation of a representative GPCR, bovine rhodopsin. Microcontact printing was used to produce micrometer-sized patterns with high contrast in receptor activity. These patterns can be used for local referencing to enhance the sensitivity of chip-based assays. The immobilized receptor was stable both for hours and during several activation cycles. A ligand dose-response curve with the photoactivatable agonist 11-cis-retinal showed a half-maximal signal at 120 nM. Our findings may be useful to develop novel assay formats for GPCRs based on receptor immobilization to solid supports, particularly to sensor surfaces.


Subject(s)
GTP-Binding Proteins/metabolism , Receptors, Cell Surface/metabolism , Surface Plasmon Resonance , Animals , Biotinylation , Cattle , Ligands , Rhodopsin/metabolism
17.
Cancer Res ; 65(3): 840-9, 2005 Feb 01.
Article in English | MEDLINE | ID: mdl-15705882

ABSTRACT

The receptor tyrosine kinase ERBB2 plays a central role in the development of breast cancer and other epithelial malignancies. Elevated ERBB2 activity is believed to transform cells by transmitting mitogenic and antiapoptotic signals. Here we show that tightly regulated overexpression of oncogenic ERBB2 in human breast carcinoma cells does not stimulate proliferation but provokes premature senescence, accompanied by up-regulation of the cyclin-dependent kinase inhibitor P21(WAF1/CIP1). A similar effect was caused by retrovirus-mediated overexpression of oncogenic ERBB2 in low-passage murine embryonic fibroblasts. In contrast to previous observations based on constitutively overexpressing cell lines, P21 induced by tetracycline-regulated ERBB2 localizes to the nucleus in arrested cells. P21 up-regulation seems to be independent of the P53 tumor suppressor protein, and senescence-associated phenotypic alterations are reversed by specific inhibition of P38 mitogen-activated protein kinases. Functional inactivation of P21 by antisense oligonucleotides is sufficient to prevent cell cycle arrest as well as the senescent phenotype, thereby identifying the P21 protein as the key mediator of hypermitogenic cell cycle arrest and premature senescence in breast carcinoma cells. Our results may thus indicate that premature senescence represents an inherent anticarcinogenic program during ERBB2-driven mammary tumorigenesis. We propose a multistep model for the process of malignant transformation by ERBB2 wherein secondary lesions either target P21 or downstream effectors of senescence to bypass this primary fail-safe mechanism.


Subject(s)
Breast Neoplasms/pathology , Cell Transformation, Neoplastic/pathology , Receptor, ErbB-2/physiology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Cycle/physiology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Nucleus/metabolism , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cellular Senescence/physiology , Cyclin-Dependent Kinase Inhibitor p21 , Gene Expression Regulation, Neoplastic , Humans , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/pharmacology , Receptor, ErbB-2/biosynthesis , Receptor, ErbB-2/genetics , Signal Transduction , p38 Mitogen-Activated Protein Kinases/physiology
18.
J Radiol ; 86(6 Pt 2): 733-46; quiz 746-7, 2005 Jun.
Article in French | MEDLINE | ID: mdl-16142068

ABSTRACT

Acute pancreatitis usually is a benign disease. However it can sometimes be severe with a 5% mortality. CT is the imaging technique of choice and should be performed in all cases. When clinical symptoms and laboratory findings are typical, the role of CT is to detect complications. In those cases, CT is ideally performed 72 hours after the beginning of symptoms. In other cases, CT can be performed earlier. The main usefulness of CT is to detect complications: necrosis, fluid collections and vascular involvement. Non-invasive imaging techniques, including US, are poorly sensitive for diagnosis of biliary pancreatitis.


Subject(s)
Diagnostic Imaging , Pancreatitis/diagnosis , Acute Disease , Diagnosis, Differential , Exudates and Transudates , Gallstones/diagnosis , Humans , Lithiasis/diagnosis , Magnetic Resonance Imaging , Necrosis , Pancreas/blood supply , Pancreatic Neoplasms/diagnosis , Pancreatitis/diagnostic imaging , Splenic Infarction/diagnosis , Tomography, X-Ray Computed , Ultrasonography , Vascular Diseases/diagnosis
19.
Struct Dyn ; 2(5): 054302, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26798825

ABSTRACT

We present a crystallography chip enabling in situ room temperature crystallography at microfocus synchrotron beamlines and X-ray free-electron laser (X-FEL) sources. Compared to other in situ approaches, we observe extremely low background and high diffraction data quality. The chip design is robust and allows fast and efficient loading of thousands of small crystals. The ability to load a large number of protein crystals, at room temperature and with high efficiency, into prescribed positions enables high throughput automated serial crystallography with microfocus synchrotron beamlines. In addition, we demonstrate the application of this chip for femtosecond time-resolved serial crystallography at the Linac Coherent Light Source (LCLS, Menlo Park, California, USA). The chip concept enables multiple images to be acquired from each crystal, allowing differential detection of changes in diffraction intensities in order to obtain high signal-to-noise and fully exploit the time resolution capabilities of XFELs.

20.
Acad Radiol ; 22(11): 1368-75, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26307028

ABSTRACT

RATIONALE AND OBJECTIVES: Living renal donors undergo an extensive examination program. These examinations should be as safe, gentle, and patient friendly as possible. To compare computed tomography angiography (CTA) and an extensive magnetic resonance imaging (MRI) protocol without contrast agents to observations from nephrectomy in living renal donors and to evaluate whether noncontrast-enhanced MRI can replace CTA for vessel assessment in living renal donors. MATERIAL AND METHODS: CTA and MRI results were compared to observations from nephrectomy, which served as the reference standard. Fifty-one potential kidney donors underwent imaging, and 31 donated a kidney. Comparisons in sensitivity, specificity, and accuracy were made with respect to the number of arteries, early branching, and the number of veins. Agreement was assessed using Cohen's kappa. The exact McNemar's test was used to test for statistically significant differences. RESULTS: In the assessment of more than one renal artery, the sensitivity and specificity of MRI and CTA were high and in perfect agreement compared to observations from surgery. The results for both MRI and CTA were as follows: (sensitivity 100%/specificity100%/accuracy 100%/Kappa = 1/P = 1). When comparing the ability to test for early branching we found, MRI: (sensitivity 33%/specificity 100%/accuracy 87%/Kappa = 0.45/P = 1) and CTA: (sensitivity 50%/specificity 100%/accuracy 90%/Kappa = 0.62/P = 1). When used to depict supernumerary veins, we found MRI: (sensitivity60%/specifivity100%/accuracy 93%/Kappa = 0.72/P = 1), whereas CTA showed: (sensitivity 40%/specificity 96%/accuracy 87% Kappa = 0.43/P = 1). CONCLUSIONS: In conclusion, an optimized MRI protocol that includes noncontrast-enhanced magnetic resonance angiography can be substituted for CTA for preoperative assessment of the renal vessels before living donor nephrectomy.


Subject(s)
Kidney Transplantation , Living Donors , Magnetic Resonance Angiography , Renal Artery/diagnostic imaging , Renal Veins/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Female , Humans , Magnetic Resonance Angiography/methods , Male , Middle Aged , Nephrectomy , Preoperative Period , Sensitivity and Specificity
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