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Biomedical subjects

F Cormier

Publications and source records attributed to F Cormier.

At least 19 recordsLinked to original sources

Constitutive STAT5 activation specifically cooperates with the loss of p53 function in B-cell lymphomagenesis.

Signal transducers and activator of transcription 5 (STAT5) A and B are transcriptional regulators that play a central role in cytokine signaling in the hematopoietic lineage and which are frequently activated in a persistent manner in human leukemia/lymphoma, as assessed by their constitutive tyrosine phosphorylation and DNA-binding activity. To study the intrinsic oncogenic properties of persistent STAT5 activation, we generated transgenic mice in which a constitutively activated point mutant of STAT5A, STAT5A(S711F), was expressed at physiological level in their lymphoid compartment. In this model, persistent STAT5 activation is weakly oncogenic, leading to the late emergence of clonal B-cell lymphoma/leukemia at a low incidence. In contrast, STAT5(S711F) was found to cooperate with the loss of function of the p53 tumor suppressor gene to both accelerate disease onset and to skew the large tumor spectrum that normally characterize p53-deficient mice to strongly favor B-cell lymphoma/leukemia. The emergence of STAT5A(S711F)-induced B-cell tumors is associated with the activation of STAT5 tyrosine phosphorylation and DNA-binding activity, indicating that activation of STAT5 oncogenic properties in transgenic STAT5A (TgSTAT5A) (S711F) mice involves the deregulation of STAT5 phosphorylation dynamics.

Animals↗

[Thirty-eight cases of dysplasia of the superior mesenteric artery].

Dysplasia of the renal and cervical arteries are well known, but dysplasia of the superior mesenteric artery (SMA) is less frequent and has specific presentation. There have been few reports on the different types of presentations. We report a series of 38 cases and present the characteristic features together with a comparison with data in the literature. These non-atheromatous non-inflammatory lesions of the arterial wall occurred either in a context of fibromuscular disease which cause is unknown (30/38 patients) or in patients with genetic disease such as neurofibromatosis (3/38) or Ehlers-Danlos disease (5/38). The fibromuscular disease presented three aspects with specific characteristics. a) stenosing lesions found predominantly in women with a different morphology than in the other localization (usually associated): irregular diffuse stenosis discovered in patients with hypertension, or ischemic digestive symptoms (6/14 patients). b) Aneurysms, also found predominantly in women, but less frequently associated with other dysplasias. These aneurysms were generally sacciform. Unlike data in the literature, our series only included rupture in 1/8 cases. The aneurysm was discovered during the exploration of abdominal pain or hypertension. c) The third type of fibromuscular disease concerned dissections which were observed in the male population, (except one case of segmental dysplasia), and presented with signs of digestive ischemia in the other seven patients, four in an emergency context requiring immediate treatment. Two genetic diseases were observed. a) Neurofibromatosis led to dysplasia analogous to fibromuscular disease, but with abnormal nerve formations in the wall. For the three cases observed, one involved only the visceral arteries and the two others thoraco-abdominal coarctation. b) We had five patients with Ehlers-Danlos syndrome, with dysplasia of the superior mesenteric artery. For three there was a fusiform dilatation and in one small aneurysms along the arterial trunk, which only required surveillance. There was only one aneurysm which required treatment by resection and venous graft. In these young patients, revascularization was generally achieved with autologous material and the prognosis was favorable. Embolization was successful in treating the sacciform aneurysm in one patient. In conclusion, dysplasia of the superior mesenteric artery has a specific presentation which must be recognized to enable diagnosis of this not uncommon condition in young subjects (even children) who often present with an acute abdomen requiring urgent treatment.

Adult↗

Embolization of hypogastric artery aneurysm: 17 cases.

Surgical management of hypogastric artery aneurysm is associated with high morbidity due to hemorrhage and ischemia. Occlusion by embolization is an attractive alternative treatment. Between 1991 and 1995, we used Gianturco coils to embolize 17 hypogastric aneurysms in 14 patients. All patients were men with a mean age of 77 years. Ten patients had previously undergone aortic repair. Complete occlusion of the aneurysm was achieved in 16 cases but placement of an iliac stent was required in 1 case. Embolization failed in one case involving rupture of a large aneurysm. No complications were observed. Moderate buttock claudication was noted after bilateral embolization in three cases. Embolization of hypogastric artery aneurysm using coils resolves the long-term problems associated with surgical ligation. Extensive aneurysm of the origin to the bifurcation is the main indication for nonresective treatment but embolization can also be a useful alternative to open surgery for high-risk patients. Availability of stent grafts may extend the indication for endovascular treatment.

Aged↗

[Post-irradiation axillo-subclavian arteriopathy: surgical revascularization].

Post-irradiation axillo-subclavian arteriopathy can develop 6 months to 20 years after radiotherapy. Incidence estimated from duplex scan screening is about 30%, half of the cases having no hemodynamic significance. In our experience, asymptomatic lesions are the most common. Nevertheless, we have observed since 1978, 38 symptomatic patients including 23 with either acute ischemia (8 patients), or chronic ischemia (15 patients) requiring revascularization. We used an endovascular approach in 8 and open surgery in 15. A bypass graft was performed in 13 patients, using a vein (8 patients) rather than a prosthesis (5 patients), implanted in healthy territory, proximally or in the common carotid (11 patients) or the proximal subclavian (2 patients), and distally in the axillary artery (5 patients) or the brachial artery (8 patients). One venous bypass became occluded postoperatively. The other bypasses remained patent during follow-up of over 10 years. There of the five prosthetic bypassess gradually failed without recurrence of critical ischemia. Other revascularization procedures included endarterectomy and thrombectomy. In the long term, functional prognosis mainly depended on the frequently associated involvement of the plexus in the post-irradiation changes, which, together with the revascularization procedure, also required neurolysis in 11 patients, two omental covers and a free musculocutaneous transfer in 9 patients.

Adult↗

TEL-JAK2 transgenic mice develop T-cell leukemia.

We previously reported a fusion between TEL and JAK2 in a t(9;12)(p24;p13) chromosomal translocation in childhood acute T-cell leukemia. This fusion gene encodes a TEL-JAK2 chimeric protein in which the 336 amino-terminal residues of TEL, including its specific self-association domain, are fused to the kinase domain of JAK2. TEL-JAK2 exhibits constitutive activation of its tyrosine kinase activity which, in turn, confers growth factor-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line. To elucidate the properties of TEL-JAK2 in primary cells and to create an animal model for TEL-JAK2-induced leukemia, we generated transgenic mice in which the TEL-JAK2 complementary DNA was placed under the transcriptional control of the EmuSRalpha enhancer/promoter. TEL-JAK2 founder mice and their transgenic progeny developed fatal leukemia at 4 to 22 weeks of age. Selective amplification of CD8-positive T cells was observed in blood, lymph nodes, thymus, spleen, and bone marrow. Expression of a tyrosine-phosphorylated TEL-JAK2 protein and activation of STAT1 and STAT5 (signal transducer and activator of transcription) were detected in leukemic tissues. TEL-JAK2 diseased mice also displayed invasion of nonhematopoietic organs, including liver, brain, lung, and kidney, by leukemic T cells. Leukemic organs of founder and transgenic progeny contained a monoclonal/oligoclonal T-cell population as analyzed by the rearrangement of the TCRbeta locus. Transplantation of TEL-JAK2 leukemic cells in nude mice confirmed their invasive nature. We conclude that the TEL-JAK2 fusion is an oncogene in vivo and that its expression in lymphoid cells results in the preferential expansion of CD8-positive T cells. (Blood. 2000;95:3891-3899)

Animals↗

Endovascular treatment of iliac aneurysms with covered stents.

The purpose of this retrospective, single-institution study was to analyze the results of endovascular treatment of iliac aneurysm using covered stents. Since January 1, 1996, a total of 34 iliac aneurysms have been treated with covered endovascular stents. The series included 9 isolated aneurysms, 29 aneurysms following repair of aortic aneurysm, and 3 false anastomotic aneurysms. The mean diameter of aneurysm was 42 mm (range, 21 to 120 mm). The aneurysm was either symptomatic or complicated in 11 cases. Three procedures were carried out under emergency conditions after acute rupture. Stent deployment was successful in 33 cases (technical success rate, 97.6%). Exclusion of the aneurysm was obtained in all cases with one (n = 26) or two overlapping (n = 7) covered stents. Mean procedure duration was 45 min (range, 25 to 75 min). The internal iliac artery was patent in 28 cases, but patency was preserved in only 4 cases. In the remaining 24 cases the internal iliac artery was excluded either preoperatively by embolization using Gianturco coils (n = 15) or intraoperatively by placement of the stent (n = 9). Endovascular treatment of iliac aneurysm with covered stents achieves good short- and middle-term results but usually requires exclusion of the internal iliac artery.

Aged↗

Antioxidant properties of crocin from Gardenia jasminoides Ellis and study of the reactions of crocin with linoleic acid and crocin with oxygen.

Crocin-a water soluble carotenoid-is found in the fruits of gardenia (Gardenia jasminoides Ellis) and in the stigmas of saffron (Crocus sativus Linne). For crocin purification, gardenia fruits are extracted with 50% acetone, followed by ether washing, ion exchange, and separation by preparative HPLC. Purified crocin with purity of >99.6% has an antioxidative activity at concentrations up to 40 ppm. At 20 ppm the antioxidative activity of crocin is comparable to that of BHA. The antioxidant property of crocin as evaluated by the thiocyanate method was better than with the thiobarbituric acid method. The adduct between the linoleic acid radical and crocin was detected by LC-MS. When crocin reacted with oxygen in the presence of FeSO(4), intermediates such as monohydroperoxides and dihydroperoxides of crocin were formed and detected by LC-MS.

Antioxidants↗

[Horton's disease and aortic aneurysm: coincidence or causality? 5 cases].

Five inflammatory aortopathies were disclosed 3 to 16 years after inaugural giant cell arteritis. Three patients were symptomatic: one aneurysm of the subrenal abdominal aorta discovered at work-up for an inferior arteriopathy, one thoraco-abdominal aneurysm with a "fissuration" episode, one calcified thoraco-abdominal aortopathy suggesting dissection. In these three cases, there was a severe inflammatory syndrome with asthenia, fever, elevated erythrocyte sedimentation rate and a large inflammatory crown around the aortopathy. In the two asymptomatic cases, the diagnosis was made during the follow-up of Horton's disease, in one patient with active disease, the other late after the initial episode. Two aneurysms required surgical cure, with resection-prosthesis of the thoraco-abdominal aneurysm and revascularization of the digestive and renal arteries. In the 4 active cases, corticosteroid therapy cured the inflammatory process both on the basis of laboratory results and the involution of the periaortic crown and, in one case, the total regression of ureteral compression causing pyeloureteral dilatation on the left. The diagnosis of giant cell arteritis was confirmed histologically in the two operated cases. Extra-cervical localizations of aortic aneurysm of dissection in patients with giant cell arteritis is not a fortuitous coincidence but an association as demonstrated by the Mayo Clinic epidemiology. On the basis of these reported cases and data in the literature, the practical conclusions are: in case of aorta involvement, particularly with inflammation in subjects under 50, giant cell arteritis should be entertained as a possible diagnosis; in patients with giant cell arteritis, follow-up should include yearly thoracic radiograms to search for thoracic aorta involvement and Doppler and ultrasound explorations to identify any abdomino-iliac lesions. This protocol is required to avoid the life-threatening complications of dissection or rupture of an aortic aneurysm.

Adrenal Cortex Hormones↗

[Popliteal venous aneurysms].

Popliteal venous aneurysms are uncommon. We reviewed 101 cases reported in the literature and our series of 11 operated cases to study the nosology and therapeutic indications. In our series, there were 7 cases of unique dystrophic aneurysms, 4 cases involving locoregional angiodysplasia: 3 cases with venous hemodynamics and 1 case with arteriovenous flow. Pulmonary embolism developed in 2 cases. Ultrasonography provided the diagnosis. A sacciform aneurysm was found in 10 cases and a fusiform aneurysm in 1 case. Venous repair was performed in all cases: 9 endoaneurysmal sutures, 1 interposition of the medial gastrocnemius vein, and 1 PTFE graft. Permeability was confirmed in all cases with no recurrent embolism. These cases and the histological correlations describe the nosology of dysplastic venous aneurysms which should be distinguished from dystrophic ectasia of incompetent veins which is not associated with pulmonary embolism. Indeed, pulmonary embolism is the most common complication revealing venous aneurysms (table I). Doppler ultrasonography can provide early diagnosis before such complications develop. Surgery is required for emergency cure in case of pulmonary embolism and is warranted for preventive cure, generally by endoaneurysmorraphic repair allowing venous permeability without the risk of iterative embolism.

Adolescent↗

[Arterial complications of neurofibromatosis].

Type 1 neurofibromatosis (NF1) is the most frequently observed phacomatosis, but involvement of arterial trunks is uncommon. Expression depends on the localization and is not easily related to the causal condition. Seven patients with type 1 neurofibromatosis developed vascular manifestations (table I) disclosed by hypertension (n = 2) digestive angina (n = 1), arterial rupture (n = 1) and aneurysm of the subrenal aorta (n = 1). The diagnosis of NF1 was clear in 5 cases; in 2 cases, the diagnosis could only be established on the basis of pathology findings demonstrating dysplasia of the media with voluminous periadventitial hypertrophic nerves (table II). All the large arteries can be involved in NF1. A complete vascular work-up is needed to identify multiple arterial localizations as found in two of our cases. Thoraco-abdominal stenosis was observed in 5 cases leading, in 2 cases, to coarctation with a hemodynamic and functional impact requiring aortic revascularization. The most frequently observed localization involves the renal arteries: 3 of our patient had occlusive lesions of the renal arteries and in 2, aneurysms were observed. Three of our patients (including 2 of the preceding), had major occlusion of digestive arteries. Three other cases revealed an aneurysm of inflammatory subrenal aorta, a rupture of the iliac into the inferior vena cava and a rupture covered by a subclavian aneurysm. The indication for surgery depends on the arterial signs of associated complications (5 of our cases). In one case surgery was indicated to prevent rupture of a splenic artery aneurysm and an aneurysm of the subrenal abdominal aorta. Two cases were treated by exclusion (ilio-cava fistula) or excision (splenic aneurysm); renal or digestive revascularization was performed with arterial or venous autografts in young patients (3 cases). One extensive abdominal coarctation was repaired with a PTFE graft as were the subclavian and subrenal aorta aneurysms. One patient with an ilio-cava fistula died from collapsus. Long-term results of the revascularizations are satisfactory with good control of the hypertension and total regression of the digestive angina. Fibrodysplasia of the renal or digestive media occurring alone or thoraco-abdominal coarctation should suggest NF1 and lead to a complete work-up to identify other arterial localizations. Patients should be followed regularly to prevent complications which in case of rupture can be life-threatening.

Adult↗

[Long-term outcome of infra-inguinal endovascular surgery for critical ischemia].

STUDY AIM: Endovascular surgery can be proposed as an alternative to infrainguinal conventional surgery in critical ischemia. The aim of this study was to report the latest results of our series of 186 patients. MATERIALS AND METHODS: One hundred and eighty-six patients (100 women and 86 men; mean age 74.5 +/- 13 years) were treated for pain during rest (31.5%), gangrene (58%), or ischemic ulcer (10.5%). The lesions were unilateral (n = 172) or bilateral (n = 14). Two hundred eighty-seven target lesions were treated: for stenosis (n = 168) or occlusion (n = 119): of superficial femoral artery (31.7%), popliteal artery (40%) or tibial arteries (28.3%). RESULTS: Technical success was achieved in 81% (15% amputations). The in-hospital mortality rate was 6.5%. The cumulative patency rate was 61 +/- 3% at 12 months, and 52 +/- 6% at 48 months. The limb salvage rate was 87 +/- 3% at 12 months and 82 +/- 4% at 48 months. Thirteen potential factors of patency were analyzed: the only predictive factors affecting patency were occlusion versus stenosis, and the use of atherectomy (Log rank test: P < 0.001 and P < 0.0001). CONCLUSION: Despite a risk of technical failure and of mid-term restenosis, endovascular surgery for critical ischemia provides a fair long-term limb salvage rate.

Aged↗

[Abdominal aortic aneurysms associated with visceral artery stenoses].

During a 6-year period six patients had combined revascularizations for an abdominal aortic aneurysm and a high-grade (> 80%) stenosis of either the superior mesenteric artery (N = 14) and/or a renal artery (N = 60 including 6 bilateral revascularizations). Revascularizations of a visceral artery were done more often with a bypass graft (N = 61) than by endarterectomy (N = 6), reimplantation (N = 4) or endovascular technique (N = 3). Fifty patients had concomitant repair of the aorta and of the visceral artery, and ten had a staged repair, favored in-high risk patients and in cases of multiple visceral artery revascularizations. Four patients (7.5%) died (2 myocardial infarctions and 2 multisystem organ failure) and twelve (20%) had a non-fatal complication in the postoperative period. Survival was 91% at one year and 81% at 5 years. Our experience emphasizes the option of a staged approach in these high-risk patients, with the availability of extra-anatomic reconstruction, and the limited value of endovascular revascularization of the visceral arteries.

Adult↗

In vitro formation of crocetin glucosyl esters by Crocus sativus callus extract.

Callus extracts of Crocus sativus exhibited the ability to transform all-trans-crocetin into its related glycosides between pH 7.0 and 7.6 in the presence of uridine-diphospho-glucose. The reactions involved the step-wise addition of a glucose moiety to a free carboxyl function and the 1-->6 addition of a glucose moiety to a glucosyl ester function. The kinetics of synthesis for each glycoside seemed to indicate that two distinct glucosyl transferases were implicated in the synthesis of crocin, all-trans-crocetin di-(beta-D-gentiobiosyl) ester.

Anticarcinogenic Agents↗

BEN/SC1/DM-GRASP, a homophilic adhesion molecule, is required for in vitro myeloid colony formation by avian hemopoietic progenitors.

BEN/SC1/DM-GRASP is a membrane glycoprotein of the immunoglobulin superfamily isolated in the chick by several groups, including ours. Its expression is strictly developmentally regulated in several cell types of the nervous and hemopoietic systems and in certain epithelia. Each of these cell types expresses isoforms of BEN which differ by their level of N-glycosylation and by the presence or absence of the HNK-1 carbohydrate epitope. In the present work, the influence of glycosylation on BEN homophilic binding properties was investigated by two in vitro assays. First, each BEN isoform was covalently coupled to microspheres carrying different fluorescent dyes and an aggregation test was performed. We found that homophilic aggregates form indifferently between the same or different BEN isoforms, showing that glycosylation does not affect BEN homophilic binding properties. This was confirmed in the second test, where the BEN-coated microspheres bound to the neurites of BEN- expressing neurons, irrespective of the isoform considered. The transient expression of the BEN antigen on hemopoietic progenitors prompted us to see whether it might play a role in their proliferation and differentiation. When added to hemopoietic progenitor cells in an in vitro colony formation assay anti-BEN immunoglobulin strongly inhibited myeloid, but not erythroid, colony formation although both types of precursors express the molecule.

Activated-Leukocyte Cell Adhesion Molecule↗

[Emboligenic aortopathies. Cholesterol embolisms: surgical treatment].

Emboligenic aortopathies are defined as lesions of the aortic wall leading to the production of thromboatheromatous material which can migrate in fragments or entirely. Emboligenic aortopathy can occur in all parts of the aorta. Localized lesions are rare and usually involve the subrenal abdominal aorta or the isthma. Diffuse lesions involving several segments of the aorta are encountered more often. There are three anatomic types of lesions: ulcerated plaques, atheromatous ulcerations, an evrysmal disease of the aorta. Therapeutic indications depend on: 1) clinical presentation: fibrinocruoric emboli, distal microemboli, disseminated cholesterol emboli; 2) the unique or multiple nature of the emboli; 3) the anatomic lesion; 4) localization.

Aortic Diseases↗

[Diabetic arteriopathy of the lower limbs].

Diabetic arteriopathy is a specific entity as it associates macro-angiopathy ischemia factor and micro-angiopathy leading to peripheral neuropathy. This association leads to specific clinical manifestations dues to interplay of ischemic and infectious phenomena. Diffuse occlusive lesions predominate distally with mediacalcosis. Wider surgical indications for revascularization of distal vessels of the leg, the ankle and the foot have reduced the number and extent of amputation. Long-term permeability after salvage surgery is identical to that in non-diabetic patients as shown by our series of 695 distal revascularizations. Endovascular techniques with or without stents or recanalization are alternatives which may be indicated in case of short occlusions or trophic disorders contraindicating surgery. Associating stents with conventional surgery may also be indicated in diabetic patients. One final progress in reducing the number of amputations has been provided by free-transfer micro-surgery techniques which allow both vascular supply and coverage of distal tissue loss.

Aged↗