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G Adam

Publications and source records attributed to G Adam.

At least 145 records · Page 8Linked to original sources

[Experimental MRI-controlled cryotherapy of the brain with almost real-time imaging by radial k-space scanning].

PURPOSE: To test radial k-space scanning by MR fluoroscopy to guide and control MR-guided interstitial cryotherapy of the healthy pig brain. METHODS: After MR tomographic planning of the approach, an MR-compatible experimental cryotherapy probe of 2.7 mm diameter was introduced through a 5 mm burr hole into the right frontal brain of five healthy pigs. The freeze-thaw cycles were imaged using a T1-weighted gradient echo sequence with radial k-Space scanning in coronal, sagittal, and axial directions. RESULTS: The high temporal resolution of the chosen sequence permits a continuous representation of the freezing process with good image quality and high contrast between ice and unfrozen brain parenchyma. Because of the interactive conception of the sequence the layer plane could be chosen as desired during the measurement. Ice formation was sharply demarcated, spherically configurated, and was free of signals. Its maximum diameter was 13 mm. CONCLUSIONS: With use of the novel, interactively controllable gradient echo sequence with radial k-space scanning, guidance of the intervention under fluoroscopic conditions with the advantages of MRT is possible. MR-guided cryotherapy allows a minimally-invasive, precisely dosable focal tissue ablation.

Animals↗

Diagnostic evaluation of malignant head and neck cancer by F-18-FDG PET compared to CT/MRI.

AIM: Evaluation of F-18-FDG PET in comparison to CT/MRI as diagnostic tool in primary and recurrent head and neck cancer. METHODS: 78 F-18-FDG PET studies were performed in 71 patients with known or suspected primary (n = 48) or recurrent (n = 30) head and neck cancer and compared to CT (n = 75) or MRI investigations (n = 3) concerning detection of the primary or recurrent tumor and detection of regional lymph node metastases in the ipsilateral and contralateral neck sides. Glucose uptake (SUV) of PET findings was correlated to tumor location, grading and dignity of the lesion. RESULTS: Sensitivity and specificity for PET in detection of primary tumors were 87%* and 67%, respectively (CT/MRI 67%* and 44%) (*p < 0.05), in detection of local recurrence 86% and 75%, respectively (CT/MRI 57% and 92%), in detection of necks affected by lymph node metastases 80% and 92%, respectively (CT/MRI 80% and 84%). Laryngeal, buccal (cheek) and salivary gland tumors had significant lower glucose uptake (SUV) when compared to tumors of the hypopharynx (p < 0.05). G1-tumors (mean SUV 4.26) had significant (p < 0.05) lower glucose uptake when compared to G2- and G3-tumors (mean SUV 7.73 and 8.19, respectively). Mean SUV of malignant PET findings (7.88) was significant (p < 0.05) higher than mean SUV of benign PET findings (5.70). However, a SUV threshold to improve diagnostic accuracy could not be defined. CONCLUSIONS: F-18-FDG PET is significantly more accurate than CT/MRI for detection of head and neck cancer. Both methods are valuable for detection of cervical lymph node metastases. Glucose uptake shows correlation to histological grading. A quantitative SUV analysis does not improve diagnostic accuracy.

Female↗

The H19 transcript is associated with polysomes and may regulate IGF2 expression in trans.

The imprinted H19 gene produces a fully processed transcript that does not exhibit any conserved open reading frame between mouse and man. Although transcriptional control elements associated with the mouse H19 locus have been shown to control the neighboring Igf2 gene in cis, the prevailing view is that the cytoplasmic H19 transcript does not display any function. In contrast to earlier reports, we show here that the H19 transcript is associated with polysomes in a variety of cell types, in both mouse and man. A possible trans-function of the H19 gene is suggested by a reciprocal correlation in trans between cytoplasmic H19 and IGF2 mRNA levels, as well as IGF2 mRNA translatability. We discuss these results in terms of their challenge to the prevailing dogma on the function of the enigmatic H19 gene, as well as with respect to the ontogeny of the Beckwith-Wiedemann syndrome, and propose that the human H19 gene is an antagonist of IGF2 expressivity in trans.

Animals↗

Accelerated proliferative senescence of rat embryo fibroblasts after stable transfection of multiple copies of the c-Myc DNA-binding sequence.

The protooncogene c-myc positively regulates cellular proliferation whereas it exhibits negative effects on both cellular senescence and differentiation. Ectopic overexpression of c-myc in transfection experiments or titration of the c-myc mRNA by antisense oligonucleotides has demonstrated that small changes of the concentration of cellular c-myc mRNA or protein levels can be crucial for these processes. In view of the role of c-Myc as a transcription factor, most of these effects may be mediated via its binding to specific DNA sequences. Here we studied the cellular reactions after manipulating the cellular concentration of c-Myc DNA-binding sites. Multiple copies of the c-Myc-binding sequence GACCACGTGGTC or, alternatively, the control sequence GACCAGCTGGTC that displays only a poor affinity for c-Myc were stably introduced into the genome of rat embryo fibroblasts. Transfection with the c-Myc-binding sequence yielded much lower clone numbers and sizes than transfection with the control sequence. After polyclonal selection and further subcultivation cells transfected with c-Myc-binding sequence exhibited a reduced growth rate and achieved less than two-thirds of the cumulative population doublings before becoming senescent and irreversibly growth arrested compared to the controls. Southern blot analysis demonstrated that 30 binding sequences on average were integrated into the cellular genome. Our results can be interpreted as competition of the ectopically introduced c-Myc-binding sequences with the functional genomic ones and assume that a fairly low number of the latter exist in the normal cellular genome. Hence, only a low copy number of introduced c-Myc-binding sequences is sufficient to cause signs of accelerated proliferative senescence.

Animals↗

Multiple pathways for regulation of the KCl-induced [3H]-GABA release by metabotropic glutamate receptors, in primary rat cortical cultures.

In rat cortical primary cultures, group II- and III-metabotropic glutamate receptor-selective agonists concentration-dependently reduced KCl-induced [3H]GABA release, with IC50 values of 11 nM for LY354740, 80 nM for L(+)-2-amino-4-phosphonobutyric acid (L-AP4), 180 nM for DCG-IV, and 330 nM for L-SOP. The group II antagonists, LY341495 and EGLU, reversed the effect of LY354740, and the group III antagonist MTPG reversed the effect of L-AP4. In the presence of omega-conotoxin GVIA, LY354740 inhibited the remaining [3H]GABA release, whereas L-AP4 was inactive. In contrast, in the presence of nifedipine, L-AP4 inhibited the remaining [3H]GABA release, but LY354740 was no longer active. The PKA inhibitor, H89, blocked the effects of both L-AP4 and LY354740, whereas the PKC inhibitor Ro 31-8220 blocked only the effect of LY354740. Both Ro 31-8220 and H89 reduced the [3H]GABA release to 60% of control. In whole-cell, voltage-clamp experiments, LY354740 and L-AP4 inhibited voltage-gated calcium channel currents with IC50 values of 28 nM and 22 microM, respectively. The results suggest that, in these cells, KCl-induced [3H]GABA release is modulated by two different mechanisms, one involving group II receptors and a direct control of the Ca2+ channel activity, and the other mediated by group III receptors and possibly involving a regulation located downstream of the Ca2+ channel activation.

Animals↗

MR-guided interstitial cryotherapy of the liver with a novel, nitrogen-cooled cryoprobe.

The purpose of the study was to test a newly developed, MR-compatible, liquid nitrogen-cooled cryoprobe. The probe has an outer diameter of 3.5 mm and was specifically developed for percutaneous, MR-guided, interstitial cryotherapy. The probe was inserted percutaneously into the livers of 10 rabbits. The cryotherapy procedure was monitored with a surface coil in a 1.5 Tesla magnet using a gradient echo sequence. Follow-up examinations were performed 3 and 7 days after the freezing procedure using T1- and T2-weighted spin echo sequences. At 7 days the animals were sacrificed and the cryolesions were examined histologically. The cryoprobe enabled artifact-free MR imaging of the "iceball" formation during freezing of the rabbit liver. After 1 min of freezing, the iceball at the tip of the probe showed an average maximum diameter of 10.8 mm. No bleeding complications were observed during or after the freezing procedure. Histologic examination 7 days after cryotherapy confirmed that the liver lesions were the same size as had been predicted by the images of the acute iceball. This new, percutaneously inserted, MR-compatible, liquid-nitrogen cooled cryoprobe allows accurate, artifact-free MR imaging of interstitial cryotherapy.

Animals↗

Spontaneous osteonecrosis of the femoral condyle: causal treatment by early core decompression.

In 16 patients with an average age of 64.6 +/- 9.8 years and sudden onset of severe knee pain, the initial stage of Ahlbäck disease (spontaneous osteonecrosis of a femoral condyle) was verified by magnetic resonance imaging (MRI) and subsequent histology. The first radiological sign of osteonecrosis (flattening of the affected femoral condyle) was present in only one case. All patients were treated surgically by extra-articular drilling into the affected femoral condyle to achieve core decompression. The knee pain disappeared immediately after surgery in all patients. Successful healing was confirmed by normalization of the bone marrow signal on MRI (on average, 35.8 months follow-up). Core decompression by extra-articular drilling into the femoral condyle can be recommended as an effective treatment in initial osteonecrosis of the knee (still radiologically invisible). However, if radiologically a flattening of the affected femoral condyle becomes apparent, progression of this disease cannot be avoided.

Aged↗

[Interventional MR tomography: equipment concepts].

Interventional MRI is one of the most recent developments of clinical MR imaging. Because of the development of open MR systems and very compact high-field systems, a number of interventional procedures are already possible today under MR control and will be tested in experimental and clinical investigations. The currently commercially available systems differ with respect to their static magnetic field strength, their gradient systems and patient access. In addition, there are differences concerning their space requirements and costs. All systems have components facilitating interventional procedures. In this article we discuss the advantages and shortcomings of these commercially available systems and look at future developments in interventional MR equipment.

Equipment Design↗

Characterization of [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine ([3H]-DCG IV) binding to metabotropic mGlu2 receptor-transfected cell membranes.

1. The binding of the new selective group II metabotropic glutamate receptor radioligand, [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine ([3H]-DCG IV), was characterized in rat mGlu2 receptor-transfected CHO cell membranes. 2. [3H]-DCG IV binding was pH-dependent, but was not sensitive to temperature. Saturation analysis showed the presence of a single binding site, with a Kd value of 160 nM and a Bmax value of 10 pmol mg(-1) protein. Binding was not sensitive to Na+-dependent glutamate uptake blockers or Cl-dependent glutamate binding inhibitors. Furthermore, up to concentrations of 1 mM, the glutamate ionotropic receptor agonists, N-methyl-D-aspartic acid (NMDA), (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate, did not affect [3H]-DCG IV binding. 3. Of the compounds observed to inhibit [3H]-DCG IV binding, the most potent were the recently described selective group II agonist, (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylate (LY 354740; Ki value 16 nM) and antagonist, 2-amino-2-(2-carboxycyclopropan-1-yl)-3-(dibenzopyran-4-yl) propanoic acid (LY 341495; Ki value 19 nM). As expected, for a G-protein-coupled receptor, guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS) inhibited [3H]-DCG IV binding in a concentration-dependent manner, with an IC50 value of 12 nNM. 4. A highly significant correlation was observed between the potencies of compounds able to inhibit [3H]-DCG IV binding and potencies obtained for agonist activity in a GTPgamma35S binding functional assay. In addition, these studies identified a number of compounds with previously unknown activity at mGlu2 receptors, including L(+)-2-amino-3-phosphonopropionic acid (L-AP3), L(+)-2-amino-5-phosphonopentanoic acid (L-AP5), 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (R-CPP), N-acetyl-L-aspartyl-L-glutamic acid (NAAG) and (RS)-alpha-methylserine-O-phosphate (MSOP).

Animals↗

Transcription of the Arabidopsis CPD gene, encoding a steroidogenic cytochrome P450, is negatively controlled by brassinosteroids.

The Arabidopsis CPD gene encodes a cytochrome P450 steroid side-chain hydroxylase (CYP90) that plays an essential role in the biosynthesis of the plant hormone brassinolide. Expression of the CPD gene is confined to cotyledons and leaf primordia in etiolated seedlings and detectable in the adaxial parenchyma of expanding leaves in light-grown plants. Transcription of the CPD gene is not affected by the plant growth factors auxin, ethylene, gibberellin, cytokinin, jasmonic acid and salicylic acid, but is specifically down-regulated by brassinolide in both dark and light. Steady-state mRNA levels of a CPD promoter-driven uidA reporter gene correlate with the expression of resident CPD gene in transgenic plants. Intermediates of the early and late C-6 oxidation pathways of brassinolide, carrying C-22 and C-23 side-chain hydroxyls, efficiently inhibit the activity of the CPD promoter. Repression of CPD transcription by brassinosteroids is sensitive to the protein synthesis inhibitor cycloheximide, indicating a requirement for de novo synthesis of a regulatory factor.

Arabidopsis↗

Characterization of (2S,2'R,3'R)-2-(2',3'-[3H]-dicarboxycyclopropyl)glycine binding in rat brain.

[(2S,2'R,3'R)-2-(2',3'-[3H]Dicarboxycyclopropyl)glycine ([3H]DCG IV) binding was characterized in vitro in rat brain cortex homogenates and rat brain sections. In cortex homogenates, the binding was saturable and the saturation isotherm indicated the presence of a single binding site with a K(D) value of 180 +/- 33 nM and a Bmax of 780 +/- 70 fmol/mg of protein. The nonspecific binding, measured using 100 microM LY354740, was <30%. NMDA, AMPA, kainate, L(-)-threo-3-hydroxyaspartic acid, and (S)-3,5-dihydroxyphenylglycine were all inactive in [3H]DCG IV binding up to 1 mM. However, several compounds inhibited [3H]DCG IV binding in a concentration-dependent manner with the following rank order of potency: LY341495 = LY354740 > DCG IV = (2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid > (2S,1'S,2'S)-2-methyl-2-(2-carboxycyclopropyl)glycine > L-glutamate = ibotenate > quisqualate > (RS)-alpha-methyl-4-phosphonophenylglycine = L(+)-2-amino-3-phosphonopropionic acid > (S)-alpha-methyl-4-carboxyphenylglycine > (2S)-alpha-ethylglutamic acid > L(+)-2-amino-4-phosphonobutyric acid. N-Acetyl-L-aspartyl-L-glutamic acid inhibited the binding in a biphasic manner with an IC50 of 0.2 microM for the high-affinity component. The binding was also affected by GTPgammaS, reducing agents, and CdCl2. In parasagittal sections of rat brain, a high density of specific binding was observed in the accessory olfactory bulb, cortical regions (layers 1, 3, and 4 > 2, 5, and 6), caudate putamen, molecular layers of the hippocampus and dentate gyrus, subiculum, presubiculum, retrosplenial cortex, anteroventral thalamic nuclei, and cerebellar granular layer, reflecting its preferential (perhaps not exclusive) affinity for pre- and postsynaptic metabotropic glutamate mGlu2 receptors. Thus, the pharmacology, tissue distribution, and sensitivity to GTPgammaS show that [3H]DCG IV binding is probably to group II metabotropic glutamate receptors in rat brain.

Animals↗

[MR-micturating cystourethrography using radical k-space sampling].

PURPOSE: To investigate the feasibility of micturating cystourethrography (MCU) by means of real-time MR imaging with radial k-space sampling. METHODS: The MR-MCU was performed in 7 adult male patients subsequent to a gadolinium(Gd)-DTPA-enhanced excretory MR-urography. The Gd-enhancement of the urethra was visualized by MR-fluoroscopy using a T1-weighted gradient-echo-sequence with radial k-space sampling and a slice thickness of 10 mm. RESULTS: The proposed technique allowed in all 7 patients a dynamic realtime imaging of the Gd-flow inside the urethra during micturition. The normal anatomy of the entire course of the urethra was demonstrated in each patient, while simultaneously the relation to the prostate and pelvic floor became visible. Furthermore, the urinary bladder could be assessed by interactive repositioning of the slice orientation in any preferred direction. The ureters could also be visualized due to the persisting Gd-enhancement of the upper urinary tract after the preceding MR-urography. CONCLUSIONS: MR-MCU using Gd-DTPA and radial k-space data acquisition is a novel imaging modality for a real-time visualization of the urethra during micturition without radiation exposure. This method also allows the assessment of the bladder, the pelvic floor, and the Gd-filled upper urinary tract which suggests a potential for the diagnosis of vesicoureteral reflux and urinary incontinence.

Adult↗

[Experimental evaluation of superparamagnetic iron oxide particles in pulmonary MR angiography].

PURPOSE: Initial experimental results of contrast-enhanced pulmonary MR angiography using the new superparamagnetic iron oxide blood pool agent FeO-BPA. METHOD: Pulmonary MRA was performed in 7 domestic pigs using a cardiac-triggered coronal T1-weighted FFE-Sequence before and up to 90 minutes after contrast injection obtained on a 1.5 T magnet with a standard gradient equipment. A dose of 4 mg Fe/kg bodyweight was used for MRA. The images were qualitatively assessed and compared with X-ray i.v.-DSA. RESULTS: The injection of FeO-BPA allows the acquisition of unsaturated in-plane images of the pulmonary vascular tree down to the first order subsegmental branches including vessel diameters of approximately 1.5 mm. In the normal non-occluded vasculature, no signal void is seen in the TE range of 2.8-5.5 ms secondary to exceeding susceptibility effects which are caused by the iron oxide accumulation. Even 90 minutes after injection of FeO-BPA, assessment of the pulmonary vasculature is still satisfactory. CONCLUSIONS: In the animal experiment, the use of the blood pool agent FeO-BPA provides detailed pulmonary angiograms even on a magnet with a conventional gradient system. The major advantage is the comfortable diagnostic window of > 1.5 hours which also portends its utility for future MR-guided pulmonary interventions.

Angiography, Digital Subtraction↗

[A new MR-(and CT-) compatible bone biopsy system: first clinical results].

PURPOSE: To describe the development and clinical evaluation of a new, hand-powered or alternatively motor-driven, MRI and CT compatible percutaneous bone biopsy system. MATERIALS AND METHODS: A new coaxial drill system (Cook Europe A/S) was designed for percutaneous, MR-guided bone biopsies and powered either by hand or an optional motor (10-250 rotations/minute using 6 bar [88.2 PSI] compressed air). The system has been used in 23 patients. Fourteen procedures were performed in a 1.5 T MR scanner (Philips-Gyroscan ACS-NT) which has an attached C-arm (Philips-BV 212-Angio) in case fluoroscopy is required, and 9 procedures in a CT scanner (Siemens-Somatom Plus). RESULTS: Driven by hand or by the pneumatic motor unit, the system achieved safe and accurate MR-guided access to all of the lesions and was even able to penetrate osteosclerotic lesions. MR- or CT-guided percutaneous biopsy yielded a correct diagnosis in all but 5 cases. No procedural complications occurred. CONCLUSION: MR-guided percutaneous bone biopsy performed with the new coaxial drill system was found to be safe and reliable, and suitable for obtaining histological specimens from skeletal lesions even when covered with thick cortical or sclerotic bone.

Biopsy↗

[Real-time MRI with radial k-radial scanning technique for control of angiographic interventions].

PURPOSE: To test the feasibility of real-time MR controlled guidance of field-inhomogeneity catheters in vitro and in vivo as a first step to MR-guided angiographic interventions. METHODS: Applying a combination of radial scanning with the sliding window reconstruction technique, a frame rate of 23 low resolution images per second was achieved. Field inhomogeneity catheters were steered through a flow phantom and into the renal arteries of a pig. RESULTS: It was possible to visualize flow or, respectively, vessels and to depict catheter movements. This enabled real-time MR-guidance of the catheter into the renal arteries of the flow phantom and into those of the pig. CONCLUSIONS: The new technique yields a sufficiently high temporal resolution for MR-guidance of catheters through vessels.

Angiography↗

[Stent placement with real time MRI guidance: initial animal experiment experiences].

PURPOSE: The aim of this study was to test the feasibility of iliac artery stent placement under MR guidance with real-time MR radial scanning in an animal model. MATERIALS AND METHODS: The experiments were performed on three pigs in a 1.5 T scanner. Radial scanning with a gradient echo technique (TR 8.4 ms, TE 3.6 ms, flip angle 10 degrees) was used. A dedicated backprojector performed the reconstruction of the raw data in real-time. The resulting MR-images were displayed on LCD screens beside the magnet. The sliding window reconstruction technique allowed image acquisition at a frame rate of 16 images per second. MR-compatible self-expanding stents with a diameter of 8 mm and a length of 3 cm were placed into the left iliac artery. Their positions were verified by digital subtraction angiography (DSA) and compared to MRI. RESULTS: All stents were successfully placed. Stent positions as monitored by real-time MR were identical to those seen on DSA images. The time needed for exact positioning of the scan plane ranged from 15 to 30 minutes. Stent placement itself took 8 minutes on average. CONCLUSION: Radial scanning applied together with the sliding window reconstruction technique allows placement of stents in iliac arteries under real-time MR control.

Angioplasty, Balloon↗