Search PubMed⌕ Search

Biomedical subjects

G Adam

Publications and source records attributed to G Adam.

At least 109 records · Page 6Linked to original sources
PubMed2001

Experimental MR imaging-guided interstitial cryotherapy of the brain.

BACKGROUND AND PURPOSE: Hyperthermal ablation techniques such as laser or RF ablation require dedicated heat-sensitive MR imaging sequences for monitoring MR imaging--guided interventions. Because cryotherapy does not have these limitations, the purpose of this study was to evaluate the feasibility of MR imaging--guided percutaneous cryotherapy of the brain. METHODS: An experimental cryoprobe with an outer diameter of 2.7 mm was inserted into the right frontal lobe of 11 healthy pigs under MR imaging control. Freezing procedures were monitored by using an interventional 1.5-T magnet and a gradient-echo sequence with radial k-space trajectories, a fast T2-weighted single-shot spin-echo sequence, and a T1-weighted single-shot gradient-echo sequence. In three animals, the procedure was also monitored by using dynamic CT. A freeze-thaw cycle with a duration of 3 minutes was repeated three times per animal. Follow-up MR images were obtained 3, 7, and 14 days after cryotherapy by using conventional MR sequences. Six animals were killed 7 days after intervention, and five animals were killed 14 days after intervention. The brains were sectioned, and the histologic findings of the lesions were compared with the MR imaging appearance. RESULTS: No artifacts due to the probe were observed on the MR images or CT scans. The ice formation (mean diameter, 12.5 mm) was very well delineated as a signal-free sphere. MR monitoring of the freezing procedure yielded a significantly higher ice:tissue contrast than did CT. The size of the ice ball as imaged by MR imaging and CT during the intervention correlated well with the MR imaging appearance of the lesions at the 14-day follow-up examination and with the histologic findings. Histologically, coagulation necrosis and gliosis were found, surrounded by a transition zone of edema and a disrupted blood-brain barrier, corresponding to a contrast-enhancing rim around the lesions on follow-up MR images. CONCLUSION: MR imaging-guided cryotherapy of the brain is possible and allows a precise prediction of the resulting necrosis. MR imaging of the freezing process does not require heat-sensitive sequences and is superior to CT for monitoring of cryoablation.

Animals↗
PubMed2001

Variability of the N-protein and the intergenic region of the S RNA of tomato spotted wilt tospovirus (TSWV).

The genetic heterogeneity of the N protein gene and the intergenic region (IGR) of the S RNA from tomato spotted wilt virus (TSWV) isolates, collected in Bulgaria, were compared with isolates from other parts of the world. The results substantiated the highly conserved nature of the N protein. Twenty six independent sequences revealed only seven variable amino acid positions, common to all isolates. The type of amino acids present in these positions seems to be independent of the geographical origin. In contrast to the structural N protein, comparisons of the related IGR-sequences led to clusters correlated with the geographical origin of the isolates. Although the overall sequence homology in the IGRs was much lower than for the N proteins, three conserved parts within this region were identified. The outstanding part was a central area of 31 nucleotides with a significantly increased GC-content. This was located in both viral- and viral-complement RNA at structures with similar foldings, which led to the assumption that this stabilised structure, rather than a sequence motive, might serve as a transcription terminator during the synthesis of the two mRNAs from the ambisense segments.

Amino Acid Sequence↗
PubMed2000

Identification of two GDP-6-deoxy-D-lyxo-4-hexulose reductases synthesizing GDP-D-rhamnose in Aneurinibacillus thermoaerophilus L420-91T.

The glycan repeats of the surface layer glycoprotein of Aneurinibacillus thermoaerophilus L420-91T contain d-rhamnose and 3-acetamido-3,6-dideoxy-d-galactose, both of which are also constituents of lipopolysaccharides of Gram-negative plant and human pathogenic bacteria. The two genes required for biosynthesis of the nucleotide-activated precursor GDP-d-rhamnose, gmd and rmd, were cloned, sequenced, and overexpressed in Escherichia coli. The corresponding enzymes Gmd and Rmd were purified to homogeneity, and functional studies were performed. GDP-d-mannose dehydratase (Gmd) converted GDP-d-mannose to GDP-6-deoxy-d-lyxo-4-hexulose, with NADP+ as cofactor. The reductase Rmd catalyzed the second step in the pathway, namely the reduction of the keto-intermediate to the final product GDP-d-rhamnose using both NADH and NADPH as hydride donor. The elution behavior of the intermediate and end product was analyzed by high performance liquid chromatography. Nuclear magnetic resonance spectroscopy was used to identify the structure of the final product of the reaction sequence as GDP-alpha-d-rhamnose. This is the first characterization of a GDP-6-deoxy-d-lyxo-4-hexulose reductase. In addition, Gmd has been shown to be a bifunctional enzyme with both dehydratase and reductase activities. So far, no enzyme catalyzing these two types of reactions has been identified. Both Gmd and Rmd are members of the SDR (short chain dehydrogenase/reductase) protein family.

Amino Acid Sequence↗
PubMed2000

Characterization of [(3)H]-LY354740 binding to rat mGlu2 and mGlu3 receptors expressed in CHO cells using semliki forest virus vectors.

The binding properties of [(3)H]-LY354740 were characterized on rat metabotropic glutamate receptors mGlu2 and mGlu3 expressed in Chinese hamster ovary (CHO) cells using Semliki Forest virus vectors. The saturation isotherm gave K(D) values of 20+/-5 and 53+/-8 nM and B(max) values of 474+/-161 and 667+/-89 fmol/mg protein for mGlu2 and mGlu3 receptors, respectively. NMDA, CaCl(2), DHPG and kainate were inactive up to 1 mM, whereas LY341495, DCG IV and ibotenate inhibited [(3)H]-LY354740 binding with similar potencies on both receptors. L-CCG I, L-AP4, L-AP5, LY354740 and 1S,3R-ACPD were 2- to 4-fold more potent inhibitors of [(3)H]-LY354740 binding to mGlu2 than mGlu3 receptors. However, MPPG and L-AP3 had a 6-fold and DTT a 28-fold preference for mGlu2 over mGlu3. ZnCl(2), at 10 mM, inhibited more than 70% of [(3)H]-LY354740 binding to mGlu2 receptors. At the same concentration it did not affect significantly [(3)H]-LY354740 binding to mGlu3 receptors. On the contrary, glutamate, quisqualate, EGLU and NAAG showed a 3-, 5-, 7- and 12-fold preference for mGlu3 over mGlu2. Finally, GTPgammaS, which partially inhibited the binding on mGlu2 receptors, was inactive to inhibit [(3)H]-LY354740 binding on mGlu3 receptors.

Amino Acids↗
PubMed2000

The synthesis and evaluation of 3-substituted-7-(alkylidene)cephalosporin sulfones as beta-lactamase inhibitors.

A series of 3-substituted-7-(alkylidene)cephaloporin sulfones were prepared and evaluated as inhibitors of representative class A and class C serine beta-lactamase. Appropriate substituents resulted in a 1000-fold improvement in the inhibition of the class A enzymes and a simultaneous 20-fold improvement in the inhibition of class C. These new compounds have achieved the goal of creating broad scale inhibitors in the cephalosporin series.

Alkenes↗
PubMed2000

A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat.

The biochemical and behavioral effects of a nonpeptidic, selective, and brain-penetrant agonist at the ORL1 receptor are reported herein. This low molecular weight compound [(1S,3aS)-8- (2,3,3a,4,5, 6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza- spiro[4. 5]decan-4-one] has high affinity for recombinant human ORL1 receptors and has 100-fold selectivity for ORL1 over other members of the opioid receptor family. It is a full agonist at these receptors and elicits dose-dependent anxiolytic-like effects in a set of validated models of distinct types of anxiety states in the rat (i.e., elevated plus-maze, fear-potentiated startle, and operant conflict). When given systemically, the compound has an efficacy and potency comparable to those of a benzodiazepine anxiolytic such as alprazolam or diazepam. However, this compound is differentiated from a classical benzodiazepine anxiolytic by a lack of efficient anti-panic-like activity, absence of anticonvulsant properties, and lack of effects on motor performance and cognitive function at anxiolytic doses (0.3 to 3 mg/kg i.p.). No significant change in intracranial self-stimulation performance and pain reactivity was observed in this dose range. Higher doses of this compound (>/=10 mg/kg) induced disruption in rat behavior. These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphanin FQ/nociceptin in adaptive behavioral fear responses to stress.

Acoustic Stimulation↗
PubMed2000

ORL1 receptor ligands: structure-activity relationships of 8-cycloalkyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-ones.

We have investigated 8-cycloalkyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-o nes as ligands for the ORL1 receptor. These unsophisticated, achiral compounds show remarkable affinity for the ORL1 receptor. Optimizing for selectivity we show that the maximum of affinity and selectivity versus the other opioid receptors is achieved for 8-cyclodecyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-o ne 2e and 8-(cis-4-isopropyl-cyclohexyl)-1-phenyl-1,3,8-triaza-spiro[4.5] decan-4-one 2q. The identified compounds (2e, 2q) are more or less equipotent to the natural ligand itself, both in the binding assay and in the functional GTPgammaS assay.

Cell Line↗
PubMed2000

High-affinity, non-peptide agonists for the ORL1 (orphanin FQ/nociceptin) receptor.

The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. These compounds exhibit high affinity for the human ORL1 receptor, exhibit moderate to good selectivity versus opioid receptors, and behave as full agonists in biochemical assays. In this paper we present the synthesis, structure-activity relationship (SAR), and biochemical characterization of substituted 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones culminating in the discovery of 8-(5-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1p, and 8-acenaphten-1-yl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 1q, two high-affinity, potent ORL1 receptor agonists with good to moderate selectivity versus the other opioid receptors.

Binding, Competitive↗
PubMed2000

Diagnosis and staging of head and neck cancer: a comparison of modern imaging modalities (positron emission tomography, computed tomography, color-coded duplex sonography) with panendoscopic and histopathologic findings.

OBJECTIVE: To compare the clinical value of positron emission tomography (PET) using fludeoxyglucose F 18, computed tomography (CT), color-coded duplex sonography (CCDS), and panendoscopy in the detection and staging of head and neck cancer. DESIGN: Prospective nonrandomized controlled study. SETTING: Medical school. PATIENTS: Convenience sample of 50 patients with suspected primary or recurrent head and neck cancer. INTERVENTION: Biopsy, tumor surgery. MAIN OUTCOME MEASURES: Information of diagnostic procedures compared with histopathologic features. RESULTS: Both PET and panendoscopy had a sensitivity of 95% and 100% for detection of primary tumor or recurrent carcinomas, respectively. Specificity for PET and panendoscopy was 92% and 85% in primary tumors and 100% and 80% in recurrent carcinoma, respectively. Sensitivity of CCDS and CT was 74% and 68% in primary tumors and 67% and 63% in recurrent carcinomas, respectively. Specificity was 75% and 69% in primary tumors and 100% and 80% in recurrent neoplasms. When assessing neck nodes, all imaging procedures exhibited identical sensitivity (84%). Specificity was 90%, 96%, and 88% in PET, CT, and CCDS, respectively. In recurrent lymph node metastases, sensitivity was 100%, 67%, and 67% and specificity was 87%, 91%, and 87% for PET, CT, and CCDS, respectively. CONCLUSIONS: Positron emission tomography was the most reliable imaging procedure in the detection of primary tumor and recurrent carcinomas localized in the head and neck region. Owing to its limited anatomical depiction, it cannot as yet replace other diagnostic procedures in preoperative planning but does contribute valuable complementary diagnostic information. Computed tomograpy may have difficulties in identifying recurrent carcinomas. For routine diagnosis of nodal spread in the neck, CCDS is recommended. Panendoscopy is a valuable diagnostic procedure that can provide key information in cases of superficial mucosal tumor involvement. Arch Otolaryngol Head Neck Surg. 2000;126:1457-1461

Biopsy↗
PubMed2000

Diagnostic and therapeutic management of lumbar and thoracic spondylodiscitis--an evaluation of 59 cases.

Fifty-nine patients with spondylodiscitis (SD) of the thoracic and/or lumbar spine were followed-up clinically and radiologically [X-ray, computed tomography (CT), magnetic resonance imaging (MRI)] over a mean time of 2.2 years (1-6.5 years). All patients without abscess formation (n = 35) were treated conservatively. Out of the group with abscess formation (n = 24) 6 patients were also treated conservatively, 11 were drained under CT control and 7 were operated. At time of diagnosis, "signs of florid inflammation" were seen in 60% of the roentgenograms, in 93% of the CTs and in all of the MRls. The sensitivity to differentiate between SD with and without abscess formation was 85% by MRI and 69% by CT. "Signs of regressive inflammation" and "signs of increasing osseous consolidation", essential facts for starting remobilization, could first be seen using CT 6 weeks after onset of therapy. Using MRI these signs were seen with a considerable delay at 12 weeks. Clinically, only 3 of the 59 analyzed patients developed recurrent SD. In conclusion, MRI is the radiological method of choice for establishing the diagnosis of SD, in particular with regard to differentiating between cases with and without abscess formations. In contrast, CT is superior for performing success control after treatment. Therapeutically, conservative, minimal-invasive and operative procedures are not rival but rather complementary.

Abscess↗
PubMed2000

Chalconoids from Fissistigma bracteolatum.

Phytochemical studies on the leaves of Fissistigma bracteolatum yielded besides the two known compounds 2-hydroxy-3,4,6-trimethoxychalcone (1) and 5,7,8-trimethoxyflav-3-ene (2), five new chalconoids 2-hydroxy-3,4,6-trimethoxychalcene (3), 2-hydroxy-3,4,6-trimethoxydihydrochalcone (4), 2'-hydroxy-3',4',6'-trimethoxydihydrochalcone (5), 2'-hydroxy-3',4',6'-trimethoxy-beta'-methoxychalcane (6) and 2'-hydroxy-3',4',6'-trimethoxy-beta'-ethoxychalcane (7). The structures of these compounds were determined by mass and NMR spectroscopic methods.

Chalcone↗
PubMed2000

Peptide-derived broad-reacting antisera against tospovirus NSs-protein.

Sequence alignments of tospovirus species of serogroup I to IV revealed a stretch of 24 amino acids at the C terminus of the non-structural protein NSs with a highly conserved sequence. Based on this sequence the 24 amino acids peptide YFLSKTLEVLPKNLQTMSYLDSIQC was synthesized and used to raise antisera in two rabbits. The specificity of the antisera against NSs from infected plants was confirmed with Western blots and by immunogold labelling and electron microscopy. These antisera detected tospovirus isolates of serogroup I to III in antigen-coated plate ELISA and Western blots but failed to detect isolates of serogroup IV. Epitope scanning using overlapping octopeptides composing the peptide suggested that the antisera contained antibodies against two different epitopes. Strongly reacting peptides were found at the C-terminus of the original peptide sequence when probing with one of the antisera. In this part the sequence was homologous to serogroup I, II and III, with all deviations from serogroup IV located here. Additional octopeptides, based on this region, synthesized with sequence modifications back to the serogroup IV sequence in all possible combinations, had low reactivity. However two of the modified peptides with partly restored serogroup IV sequences revealed promising reactivity and could be suitable to raise an antiserum with broader reactivity, including serogroup IV.

Amino Acid Sequence↗
PubMed2000

Synthesis of (1S,3aS)-8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4. 5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonist with anxiolytic-like properties.

The development of 8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen1-yl)-1-phenyl-1,3,8-triaza-spiro[4. 5]decan-4-ones 3 starting from (RS)-8-acenaphten-1-yl-1-phenyl-1,3, 8-triazaspiro[4.5]decan-4-one 1 is reported. The synthesis and the binding affinities at human OFQ and opioid (micro, kappa, delta) receptors of the stereoisomers 3a-f are described. In vitro the most selective compound, (1S,3aS)-8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen1-yl)-1-phenyl-1,3,8-triaza-spiro[4. 5]decan-4-one 3c, was found to act as a full agonist at the OFQ receptor in the GTPgamma(35)S binding test. It turned out to be selective versus a variety of other neurotransmitter systems. When tested in vivo following intraperitoneal injection, compound 3c was found to decrease neophobia in a novel environment and to exhibit dose-dependent anxiolytic-like effects in the elevated plus-maze procedure, thus confirming the effects observed following intracerebroventricular infusion of the OFQ peptide in rat.

Alprazolam↗
PubMed2000

Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections.

We have investigated the binding properties of [(3)H]quisqualate to rat metabotropic glutamate (mGlu) 1a and 5a receptors and to rat and human brain sections. Saturation isotherms gave K:(D) values of 27 +/- 4 and 81 +/- 22 nM: for mGlu1a and mGlu5a receptors, respectively. Several compounds inhibited the binding to mGlu1a and mGlu5a receptors concentration-dependently. (S:)-4-Carboxyphenylglycine, (S:)-4-carboxy-3-hydroxyphenylglycine, and (R,S)-1-aminoindan-1,5-dicarboxylic acid, which completely inhibited [(3)H]quisqualate binding to the mGlu5a receptor, were inactive in a functional assay using this receptor. The distribution and abundance of binding sites in rat and human brain sections were studied by quantitative receptor radioautography and image analysis. Using 10 nM: [(3)H]quisqualate, a high density of binding was detected in various brain regions with the following rank order of increasing levels: medulla, thalamus, olfactory bulb, cerebral cortex, spinal cord dorsal horn, olfactory tubercle, dentate gyrus molecular layer, CA1-3 oriens layer of hippocampus, striatum, and cerebellar molecular layer. The ionotropic component of this binding could be inhibited by 30 microM: kainate, revealing the distribution of mGlu1+5 receptors. The latter were almost completely inhibited by the group I agonist (S:)-3,5-dihydroxyphenylglycine. The binding profile correlated well with the cellular sites of synthesis and regional expression of the respective group I receptor proteins revealed by in situ hybridization histochemistry and immunohistochemistry, respectively.

Animals↗
PubMed2000

[Radial k-scanning for real-time MR imaging of central and peripheral pulmonary vasculature].

PURPOSE: To depict the central and peripheral pulmonary vessel anatomy with real-time radial MR scanning without respiratory control. METHODS: Three healthy volunteers and one patient with pulmonary embolism proven by spiral CT angiography were studied with a 1.5 T MR imaging system. First, a breath-hold, contrast-enhanced MR angiography was performed for comparison of accuracy. Gradient echo images (TR 16 ms, TE 4 ms, flip angle 18 degrees) were obtained applying a combination of radial scanning and the sliding window reconstruction technique. A dedicated back-projector allowed data reconstruction in real-time with a frame rate of 20 images per second. Scanning was performed during free breathing. RESULTS: The described technique depicted the central and peripheral portions of the normal pulmonary anatomy with comparable image quality as the 3D contrast-enhanced angiography. Visualization of the pulmonary emboli as demonstrated by spiral CT was possible. CONCLUSION: Real-time radial scanning allows promising image acquisition of the pulmonary vasculature without respiratory control. Further technical improvements and clinical trials are required to evaluate its role in the diagnosis of vascular pathologies.

Adult↗
PubMed2000

[Interventional magnetic resonance imaging--non-invasive imaging for interventions].

As a prerequisite for MR-guidance of interventional procedures, instruments have to be well depicted in the MR image without obscuring or distorting the underlying anatomy. For non-vascular interventions the imaging speed has to be in the range of seconds while control of vascular interventions requires real time imaging speed. The imaging contrast has to be maintained as well as a high spatial resolution. Furthermore, sufficient patient access has to be provided by the MR scanner. Neither an ideal magnet nor the optimal single sequence are available to fulfill the above-mentioned criteria. The type of sequence--gradient echo versus spin echo--together with changing of the echo time and phase encoding direction will ensure an appropriate size of the artifact and thereby of the appearance of the instrument in the MR image. The feasibility of non-vascular MR-guided interventions has been proved at field strengths ranging from 0.064 T to 1.5 T. Bone biopsies, soft tissue biopsies, drainages, and control of interstitial thermo- and cryotherapy have been reported. For vascular interventions, different real time MR strategies are currently under investigation. The development of dedicated catheters and guide wires has enabled MR-guided dilatations, stenting, placement of vena cava filters, and TIPS procedures. Considering the fast progress being made in this field, there can be no question that interventional MRI will become a well-accepted clinical tool offering potential advantages such as excellent soft tissue contrast, multiplanar imaging, flow measurements, high resolution imaging of vessel walls, and lack of ionizing radiation.

Artifacts↗