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Biomedical subjects

G Adam

Publications and source records attributed to G Adam.

At least 19 recordsLinked to original sources
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

[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↗
PubMed1999

The addition of cisplatin to cyclophosphamide-doxorubicin-etoposide combination chemotherapy in the treatment of patients with small cell lung carcinoma: A randomized study of 457 patients. "Petites Cellules" Group.

BACKGROUND: To assess whether the addition of cisplatin (100 mg/m(2) administered intravenously on Day 1) to CDE (cyclophosphamide [1000 mg/m(2) on Day 1], doxorubicin [45 mg/m(2) on Day 1], and etoposide [150 mg/m(2) on Days 1 and 2] combination is useful in the treatment of patients with small cell lung carcinoma (SCLC). METHODS: In a multicenter clinical trial, 457 patients were randomized from May 1988 to March 1993 to receive either CDE (n = 228) or cisplatin-CDE (PCDE, n = 229) chemotherapy every 4 weeks for 6 cycles. As patients with limited SCLC were included in a concomitant trial assessing thoracic radiotherapy, the current study mainly included patients with extensive stage (79%) or limited stage disease and a contraindication for thoracic radiotherapy. RESULTS: The objective response rate was higher in the cisplatin-CDE group (72%) than in the CDE group (53%) (P = 0.0001). The median overall survival was similar for the groups that received CDE (266 days) and PCDE (271 days) (P = 0.93, log rank test). A higher fatal neutropenia rate was observed in the PCDE group (n = 23) than in the CDE group (n = 4) (P < 0.001, log rank test), mainly for patients with extensive disease (n = 26; P = 0.015, log rank test). CONCLUSIONS: The addition of cisplatin to a CDE regimen is toxic to patients with extensive SCLC and does not improve overall survival. The PCDE combination must be avoided for patients with extensive SCLC; CDE or cisplatin-etoposide combinations remain standard chemotherapy for these patients. The PCDE combination associated with granulocyte-colony stimulating factors could only be assessed in patients with good prognoses.

Aged↗
PubMed1999

8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one derivatives as orphanin FQ receptor agonists.

A series of 8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan+ ++-4-one derivatives 1 was studied with respect to the binding affinity for the orphanin FQ (OFQ) and opioid (mu, kappa, delta) receptors. The influence of stereochemistry as well as the substitution pattern of the phenyl-ring in position 1 on the affinity for the orphanin FQ receptor and selectivity to opioid (mu, kappa, delta) receptors is discussed. The most interesting compound 1c was tested for its anxiolytic-like properties in vivo.

Animals↗
PubMed1999

Inactivation of brassinosteroid biological activity by a salicylate-inducible steroid sulfotransferase from Brassica napus.

Recent discoveries from brassinosteroid-deficient mutants led to the recognition that plants, like animals, use steroids to regulate their growth and development. We describe the characterization of one member of a Brassica napus sulfotransferase gene family coding for an enzyme that catalyzes the O-sulfonation of brassinosteroids and of mammalian estrogenic steroids. The enzyme is specific for the hydroxyl group at position 22 of brassinosteroids with a preference for 24-epicathasterone, an intermediate in the biosynthesis of 24-epibrassinolide. Enzymatic sulfonation of 24-epibrassinolide abolishes its biological activity in the bean second internode bioassay. This mechanism of hormone inactivation by sulfonation is similar to the modulation of estrogen biological activity observed in mammals. Furthermore, the expression of the B. napus steroid sulfotransferase genes was found to be induced by salicylic acid, a signal molecule in the plant defense response. This pattern of expression suggests that, in addition to an increased synthesis of proteins having antimicrobial properties, plants respond to pathogen infection by modulating steroid-dependent growth and developmental processes.

Amino Acid Sequence↗
PubMed1999

The synthesis and evaluation of 6-alkylidene-2'beta-substituted penam sulfones as beta-lactamase inhibitors.

Penicillin sulfones, which structurally incorporate both a 6-position alkylidene substituent and a 2'beta substituent, have been synthesized and evaluated as inhibitors of class C and class A serine beta-lactamases. Incorporation of the 2'beta-substituent generally improves inhibitory activity. Substituents that improve transport across the bacterial cell membrane have also been incorporated.

Cloxacillin↗
PubMed1999

Structure-activity relationships of substituted 5H-thiazolo[3,2-a]pyrimidines as group 2 metabotropic glutamate receptor antagonists.

A series of 5H-thiazolo[3,2-a]pyrimidine derivatives 1 was studied with respect to the inhibition of 1S,3R-ACPD (10 microM)-stimulated GTP gamma35S binding on rat mGlu2 receptor transfected cell membranes. The influence of substituents at position 6 and 7 as well as the substitution pattern of the two phenyl-rings in position 2 and 5 on the activity is discussed.

Animals↗
PubMed1999

Determination of copy number of c-Myc protein per cell by quantitative Western blotting.

The protooncogene c-Myc plays a key role in growth control, differentiation, and apoptosis. An abnormally high expression of c-myc has been found to be associated with many neoplasms. c-Myc gene expression is usually measured at the mRNA level. Few studies have been published on quantitative Myc protein determination. A major drawback of ELISA (enzyme-linked immunosorbent assay) methods is the uncertainty of the specificity of the antibody reaction. In contrast, antibody specificity can be easily controlled by Western/immunoblotting. Here we describe a method to quantify c-Myc protein in primary human IMR90 lung fibroblasts based on Western blotting. Using a high-resolution polyacrylamide gel, we were able to differentiate the cellular c-Myc protein (64 kDa) from a c-Myc internal standard (65 kDa). We determined both the total c-Myc protein content per cell and its distribution in the cytoplasmic and nuclear fractions. About 4000 c-Myc protein molecules were detected in the cytoplasmic fraction and 29,000 copies in the nuclear fraction for proliferating human lung fibroblasts IMR90. The ratio of nuclear (active) to cytoplasmic (inactive) c-Myc protein changed from 17:1 for proliferating cells to 2.5:1 for confluent cells.

Blotting, Western↗
PubMed1999

Brassinosteroids.

Explore the source record for details and available documents.

Brassinosteroids↗
PubMed1999

Interventional MR imaging: percutaneous abdominal and skeletal biopsies and drainages of the abdomen.

Since the introduction of open magnets and short-bore closed magnets, and the availability of fast imaging sequences, MR imaging has become a tool for guidance and control of percutaneous nonvascular and vascular procedures. In general, percutaneous biopsies or drainages require no specific hardware or software modifications. For lesion localization and control of the needle track, simple fast imaging sequences such as fast T1-weighted gradient-echo techniques or fast single-shot T2-weighted spin-echo sequences are sufficient and can be applied depending on the best tissue-to-lesion contrast. Typical scan times range from 1 to 3 s. Different types of biopsy needles are commercially available, allowing sampling of sufficient amounts of tissue. For drainage procedures non-ferromagnetic materials, such as nitinol wires, should be preferred to minimize image distortion by metallic artifacts. Indications for percutaneous biopsies include subdiaphragmatic liver lesions, lesions poorly visible on ultrasound or contrast-enhanced computed tomography, and lesions of the bone marrow characterized by an unspecific bone marrow edema. For percutaneous drainages, subdiaphragmatic lesions appear to be a good indication. With some experience the procedure time is not longer than that under CT or US guidance.

Abdomen↗
PubMed1999

The genotype and epigenotype synergize to diversify the spatial pattern of expression of the imprinted H19 gene.

Little is known of how the genetic background effects the phenomenon of genomic imprinting. The H19 gene belongs to a cluster of imprinted genes on human chromosome 11. Here we show that the alternative splicing of a human H19 transcript is genotype-specific. Moreover, this variant transcript, which lacks exon 4, is either not found at all, is widely expressed or is confined to extra-villous cytotrophoblasts in first trimester placenta, depending on a combination of the genotype and the sex of the transmitting parent.

Alleles↗
PubMed1999

Verb agreement morphology in Hebrew-speaking children with specific language impairment.

Earlier reports of verb morphology use by Hebrew-speaking children with specific language impairment (SLI) have suggested that these children mark agreement with the subject as accurately as younger control children matched according to mean length of utterance (MLU). This issue was examined in greater detail in the present study by including a wider range of agreement inflections from the present and past tense paradigms and employing verbs of different patterns (binyanim). It was hypothesized that children with SLI would be more limited than would MLU controls in their use of agreement inflections within past tense because the past tense agreement paradigm of Hebrew requires the simultaneous manipulation of three features-person, number, and gender. Differences between the groups were not expected for the use of agreement inflections within present tense, because only two features-number and gender-must be manipulated in the present tense paradigm. A group of preschool-age children with SLI was found to have more difficulty than did MLU controls in the use of most past tense agreement inflections. Within present tense, the two groups differed in their use of agreement inflections in only one pattern. For both groups, most errant productions differed from the target form by only one feature, usually person or tense. We found no feature that was consistently problematic for the children. The findings are discussed within a limited processing capacity framework.

Adult↗
PubMed1999

[MR defecography at 1.5 Tesla with radial real-time imaging and reduced image field].

PURPOSE: To evaluate a new technique for MR defecography with real-time imaging using radial k-space profiles. MATERIALS AND METHODS: A catheter-mounted condom was inserted into the rectum of 16 patients and filled in situ by a mixture of Nestargel and Gadolinium. After multiplanar imaging of the pelvis by high resolution T2-weighted turbo-spin echo sequences, defecation was imaged by a gradient echo sequence with radial k-space filling using a reduced field of view (rFOV) in real-time. The documentation was performed on an S-VHS recorder. RESULTS: At a constant background signal, radial k-space filling yields a real-time impression. An interactive software allowed the operator to modify the slice thickness, slice plane, flip angle and slice angulation during scanning, resulting in an optimum imaging quality of the defecation. CONCLUSIONS: This new imaging technique allows real-time MR defecography in a high-field scanner and provides all anatomical und functional information of the defecation.

Adult↗
PubMed1999

[CT-guided percutaneous biopsies for the classification of focal liver lesions: a comparison between 14 G and 18 G puncture biopsy needles].

PURPOSE: Analysis and comparison of CT-guided 14- and 18-gauge cutting needle biopsies to accurately assess focal liver disease. METHODS: The data of 272 CT-guided biopsies in 268 patients were evaluated retrospectively with regard to sensitivity, specificity and complication rate of the chosen needle caliber in differentiating between benign and malignant disease as well as in the ability to determine specific cell types in the various disorders. A 14-gauge (G) needle was used in 101 (37.1%) cases, an 18-g needle biopsy was performed in 171 (62.9%) cases. The Fisher exact test was employed for statistical analysis. RESULTS: Cutting needle biopsy yielded sufficient histologic material in 267 of 272 (98.2%) cases. Correct diagnosis of malignancy was established in 178 of 191 (93.2%) lesions, 73 of 76 (96.1%) disorders were accurately defined as benign, resulting in an overall value of 94.0% (251 of 267). Of these 251 biopsies a definite histological diagnosis could be determined in 90.6% of the cases employing a 14 G needle and in 90.3% using an 18-g needle. The sensitivity, specificity and rate of complications were 94.8%, 92.0%, 3.0% for the 14-g needle and 92.7%, 97.6%, 0.6% for the 18-g needle, respectively. There were no statistically significant differences with regard to the needle size. CONCLUSIONS: CT-guided biopsy of hepatic lesions with the 18-g biopsy needle is of equivalent diagnostic accuracy when compared with the 14-g needle.

Adult↗
PubMed1999

Successful treatment of pulmonary Mycobacterium xenopi infection in a natural killer cell-deficient patient with clarithromycin, rifabutin, and sparfloxacin.

Isolation of Mycobacterium xenopi from the respiratory tract may indicate pneumonia, often clinically indistinguishable from tuberculosis. Resistance to the classic antituberculous drugs renders the treatment of these infections problematic. We report on a case of cavernous pneumonia caused by M. xenopi in a 36-year-old male with natural killer cell deficiency but without severe immunodeficiency. He was successfully treated with a novel triple-drug combination comprising clarithromycin, sparfloxacin, and rifabutin. An impressive subsequent regression of pathological pulmonary changes was observed, and mycobacteria could no longer be detected. The therapeutic potential of clarithromycin and sparfloxacin in the treatment of M. xenopi infections is discussed.

Adult↗
PubMed1999

[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↗