We have characterized a novel mutation of the human AR, G577R, associated with partial androgen insensitivity syndrome. G577 is the first amino acid of the P box, a region crucial for the selectivity of receptor/DNA interaction. Although the equivalent amino acid in the GR (also Gly) is not involved in DNA interaction, the residue at the same position in the ER (Glu) interacts with the two central base pairs in the PuGGTCA motif. Using a panel of 16 palindromic probes that differ in these base pairs (PuGNNCA) in gel shift experiments with either the AR DNA-binding domain or the full length receptor, we observed that the G577R mutation does not induce binding to probes that are not recognized by the wild-type AR. However, binding to the four PuGNACA elements recognized by the wild-type AR was affected to different degrees, resulting in an altered selectivity of DNA response element recognition. In particular, AR-G577R did not interact with PuGGACA palindromes. Modeling of the complex between mutant AR and PuGNACA motifs indicates that the destabilizing effect of the mutation is attributable to a steric clash between the C beta of Arg at position 1 of the P box and the methyl group of the second thymine residue in the TGTTCPy arm of the palindrome. In addition, the Arg side chain can interact with G or T at the next position (PuGCACA and PuGAACA elements, respectively). The presence of C is not favorable, however, because of incompatible charges, abrogating binding to the PuGGACA element. Transactivation of several natural or synthetic promoters containing PuGGACA motifs was drastically reduced by the G577R mutation. These data suggest that androgen target genes may be differentially affected by the G577R mutation, the first natural mutation characterized that alters the selectivity of the AR/DNA interaction. This type of mutation may thus contribute to the diversity of phenotypes associated with partial androgen insensitivity syndrome.

Amino Acid Sequence↗

PubMed2001

[Coronary steal syndrome by systemic pulmonary hypervascularization fed by a mammary-left anterior descending artery bypass. Treatment by embolization].

We report a case of coronary-steal syndrome which occurred after coronary bypass surgery. It was related to systemic hypervascularization of the lung caused by a bronchopathy. The steal syndrome was fed by an ectopic bronchial artery arising from the internal mammary--left anterior descending artery bypass graft. The myocardial ischemia disappeared after hyperselective embolization of the ectopic bronchial artery. The authors outline the rarity of this syndrome and its pathophysiology. They insist on the necessity to perform broncho-systemic arteriography for candidates to coronary surgery, in patients with thoracic diseases which can induce systemic hypervascularization of the lung.

Bronchial Arteries↗

PubMed2001

[Percutaneous radiofrequency ablation of liver tumors].

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Diagnostic Imaging↗

PubMed2000

Aspartate 351 of estrogen receptor alpha is not crucial for the antagonist activity of antiestrogens.

The antagonist activity of antiestrogens is due to the presence of a long carbon side chain at positions 7alpha or 11beta or equivalent on their steroid or steroid-like skeletons. These side chains establish hydrophobic interactions with amino acids of the estrogen receptor alpha (ERalpha) ligand binding domain. In addition, a hydrogen bond formed between amino acid Asp-351 and the tertiary amine present at the end of the side chain of partial antiestrogens is considered to be crucial for their antiestrogenicity. Here, we have investigated the role of Asp-351 in antiestrogen action in transiently transfected HeLa and MDA-MB-231 cells. Our results indicate that disruption of the negative charge at position 351 does not increase the agonist activity of partial antiestrogens and thus that the hydrogen bond with the antiestrogen side chain is not determinant in positioning the side chain in an antagonist position. The negative charge at position 351 was not required for transcriptional activity in the presence of hormone, but its presence was necessary for basal activity of the wild-type receptor and constitutive activities of mutants L536P and Y537A, suggesting a role of Asp-351 in stabilizing the active conformation of ERalpha. This stabilizing role of Asp-351 could be due to interaction of Asp-351 with the amide group of the peptide bond between Leu-539 and Leu-540 in helix 12 observed in the active conformation of the ERalpha ligand binding domain.

Animals↗

PubMed2000

Implanted central venous catheter-related acute superior vena cava syndrome: management by metallic stent and endovascular repositioning of the catheter tip.

We describe a case of a 49-year-old woman with stage-IIIB lung adenocarcinoma who experienced an acute superior vena cava syndrome related to an implanted central venous catheter without associated venous thrombosis. The catheter was surgically implanted for chemotherapy. Superior vena cava syndrome appeared after the procedure and was due to insertion of the catheter through a subclinical stenosis of the superior vena cava. Complete resolution of the patient's symptoms was obtained using stent placement and endovascular repositioning of the catheter tip.

Acute Disease↗

PubMed2000

Abdominal aortic aneurysm: pretherapy assessment with dual-slice helical CT angiography.

OBJECTIVE: The purpose of this study was to evaluate dual-slice helical CT in the pretherapy assessment of abdominal aortic aneurysms. SUBJECTS AND METHODS: Dual-slice helical CT angiography was performed in 47 consecutive patients (mean age, 59 years) with abdominal aortic aneurysm to determine whether we could then evaluate the extent of aneurysm and see associated renal, celiac, mesenteric, and iliofemoral artery disease. Results were compared with those of digital subtraction angiography (n = 47) and surgery (n = 37). RESULTS: The proximal and distal extents of abdominal aortic aneurysm correlated well with surgical findings. Dual-slice helical CT showed all main (n = 102) and accessory (n = 13) renal arteries with a sensitivity of 91% and a specificity of 100% for revealing associated renal artery stenosis exceeding 50%. Sensitivity and specificity of dual-slice helical CT for revealing stenosis exceeding 75% in celiac and superior mesenteric arteries were both 100%. Three of four iliofemoral artery stenoses and two occlusions of the common iliac artery were revealed by dual-slice helical CT. CONCLUSION: Helical CT angiography with dual-slice scanning is a useful and minimally invasive technique that can provide with high accuracy all the necessary information for treatment of abdominal aortic aneurysm.

Adult↗

PubMed2000

[Imaging features of gastric stromal tumors: radiologic-pathologic correlation. Report of 4 cases].

GOAL: This study concerns the new anatomo-pathologic semantics of the ancient gastric leiomyoblastoma that become gastric stromal tumors (GST) and identified as stemming of "pace-maker" cells of Cajal related to the immunohistochemical characterization of the phenotype. MATERIAL: and methods. We limited the study to the mesenchymatous tumors to "pacemaker" cells. For this purpose, we report four documented observations of gastric stromal tumors correlated to the histology and to the immunohistochemical study. RESULTS: Although some signs are often described (exogastric development, heterogeneity with cystic and necrotic component, predominating peripheral enhancement...), radiological aspects of these tumors are not specific because, analogues to the other mesenchymal tumors (leiomyoma or schwannoma). The topographic diagnosis is difficult, realized by echoendoscopy, CT scan and MRI. The irregularity of contours evokes the malignancy as hemoperitoneum. GST do not show lymphophilic behavior that differentiates them from the adenocarcinomas and gastric lymphomas. The surgical treatment is the best treatment, allowing the immuno-histological diagnosis of certainty from the complete operative specimen. CONCLUSION: Some tumors are difficult in classifying despite classic histology necessitating immunohistochemical tests for the identification of muscular, nervous, autonomous nervous system flexion of mesenchymatous tumors with epithelioid or spindle cells of the gastrointestinal tract. Then a radio-clinical follow-up is therefore indicated: the evolution is the alone real marker of malignancy.

Aged↗

PubMed2000

[Intralobar sequestration of the lung in an adult (type 1 of pryce). Treatment by coil embolization].

A 34 year old patient presented with recurrent hemoptysis. A chest radiograph was normal. Helical CT angiogram of the chest with tridimensional reconstructions demonstrated an intralobar pulmonary vascular sequestration Pryce I-type of the right lower lobe. The angiography confirmed the diagnosis showing a large feeding artery arising from the coeliac trunk. An embolization of the feeding artery using metallic coils was performed. Transient pulmonary infarction occurred immediately after treatment. At two years follow-up, the patient remains asymptomatic. Percutaneous embolization of this rare pulmonary vascular malformation is an alternative to surgical treatment.

Adult↗

PubMed1999

Life-threatening spontaneous psoas haematoma treated by transcatheter arterial embolization.

We report two cases of large spontaneous psoas haematoma in patients on anticoagulant therapy. Active bleeding was well demonstrated on spiral CT. Transcatheter arterial embolization was used successfully to stop bleeding. The diagnostic strategy, the relevance of spiral computed tomography and our therapeutic approach to this complication are discussed.

Aged↗

PubMed1999

Helical CT phlebography of the superior vena cava: diagnosis and evaluation of venous obstruction.

OBJECTIVE: The purpose of this study was to determine the feasibility of helical CT phlebography of the superior vena cava (SVC) and to evaluate the role of this imaging technique in the diagnosis and treatment of SVC obstruction. SUBJECTS AND METHODS: Twenty-three helical CT phlebograms were obtained of patients with clinical findings that were suggestive of SVC obstruction (n = 19) and of patients undergoing posttherapeutic evaluation for SVC obstruction (n = 4). CT examinations consisted of helical acquisitions obtained in the craniocaudal direction with simultaneous bilateral antecubital vein injection of 2 x 90 ml of 12% iodinated contrast material at 2 ml/sec. Combined analysis of axial, multiplanar, and maximum-intensity-projection reformatted images was used for all patients. Image quality, venous stenosis or obstruction, intraluminal thrombus, and collateral pathways were evaluated. Comparison with digital phlebographic data was available for 16 patients; this comparison was performed in a nonblinded manner. RESULTS: CT phlebograms were considered technically optimal in 91% of the patients. In all these patients, helical CT phlebograms showed the venous obstruction: the site, extent, cause, and collateral pathways. CT phlebography appeared to be well correlated with digital phlebography in 16 patients regarding the degree of obstruction, the presence of collateral pathways, and the presence of thrombus. CONCLUSION: Helical CT phlebography may be a useful technique for imaging the SVC and its tributaries. This imaging technique is simple to perform and can provide all the information necessary to diagnose and treat SVC obstruction.

Feasibility Studies↗