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Biomedical subjects

Laurent Chiche

Publications and source records attributed to Laurent Chiche.

At least 19 recordsLinked to original sources
PubMed2006

Adrenocortical carcinoma extending into the inferior vena cava: presentation of a 15-patient series and review of the literature.

BACKGROUND: Involvement of the inferior vena cava (IVC) is a controversial risk factor for surgical treatment of adrenocortical carcinoma (ACC). This study aims to assess the outcome of an aggressive surgical policy for ACC extending into the IVC and discuss treatment strategies based on a review of the literature. METHODS: Over a 25-year period, 15 patients were treated for ACC extending into the IVC. The upper limit of the extension was the infrahepatic IVC in 2 patients, retrohepatic IVC in 6, and suprahepatic IVC in 7, including 4 with extension into the right atrium. Seven patients presented with concurrent metastases. The operative technique was thrombectomy (n = 13), partial resection with direct closure (n = 1), and total resection with replacement of the IVC (n = 1). Venous control was achieved by caval clamping alone (n = 4), hepatic vascular exclusion (n = 5), and the use of normothermic cardiopulmonary bypass or hypothermic circulatory arrest (n = 6). RESULTS: Two patients died postoperatively. Ten patients died of metastatic complications at 4 to 31 months. Median survival time was 8 months. Three patients were still alive after 24, 25, and 45 months of follow-up, one of whom was reoperated at 17 months for a local recurrence. No evidence of recurrent intravenous involvement was found during follow-up in any patient in whom complete resection was achieved. CONCLUSIONS: Our findings suggest that surgical treatment can be effective for management of ACC with extension into the IVC. Long-term prognosis is poor owing to delay in diagnosis, frequent associated metastatic disease and lack of effective adjuvant treatment.

Adolescent↗
PubMed2006

Leiomyosarcoma of the inferior vena cava: experience in 22 cases.

From 1979 to 2004, 22 patients were seen with leiomyosarcomas of the inferior vena cava (IVC). Twenty were treated surgically. Involvement of the IVC included the infrarenal segment in 3 cases, the suprarenal and/or retrohepatic segment in 13, and the suprahepatic segment in 4. Nineteen patients underwent wide tumor resection followed by ligation of the IVC in 5 cases, replacement with a PTFE prosthesis in 13, and cavoplasty in 1. An intracardiac tumor extension was resected during hypothermic circulatory arrest in 1 patient. Vascular exclusion of the liver was used in 5 cases and simple clamping of the IVC in 13 cases. There were 1 intraoperative death due to cardiac failure and 3 postoperative deaths due to multiple organ failure, liver failure, and duodenal fistula after treatment of a bleeding ulcer. Fifteen of the 16 surviving patients underwent adjuvant chemotherapy associated with radiation therapy in 4 cases. One patient was lost from follow-up at 10 months. Four patients including one with metastasis are still alive with a mean follow-up of 18.3 months. Eleven patients died after a mean follow-up period of 43.7 months due to local recurrence and/or distant metastasis in 9 cases and complications of chemotherapy in 2. The 3- and 5-year mean actuarial survival rates in patients who underwent resection were 52.0% and 34.8%, respectively. Leiomyosarcoma of the IVC is a serious disease. Although surgical resection combined with chemotherapy is usually not curative, it can achieve reasonably long-term survival. We recommend aggressive operative management using the latest vascular surgery and oncology techniques.

Adult↗
PubMed2005

The betaalphabetaalphabeta elementary supersecondary structure of the Rossmann fold from porcine lactate dehydrogenase exhibits characteristics of a molten globule.

Protein classifications show that the Rossmann fold, which consists of two betaalphabetaalphabeta motifs (BABAB) related by a rough twofold axis, is the most populated alphabeta fold, and that the betaalphabeta submotif (BAB) is a widespread elementary structural arrangement. Herein, we report MD simulations, circular dichroism and NMR analyses on BAB and BABAB from porcine lactate dehydrogenase to evaluate their intrinsic stability. Our results demonstrate that BAB is not stable in solution and is not a folding nucleus. We also find that BABAB, despite its appearance of a functional and structural unit, is not an independent and thermodynamically stable folding unit. Rather, we show that BABAB retains most native secondary structure but very little tertiary structure, thus displaying characteristics of a molten globule.

Animals↗
PubMed2005

PAT: a protein analysis toolkit for integrated biocomputing on the web.

PAT, for Protein Analysis Toolkit, is an integrated biocomputing server. The main goal of its design was to facilitate the combination of different processing tools for complex protein analyses and to simplify the automation of repetitive tasks. The PAT server provides a standardized web interface to a wide range of protein analysis tools. It is designed as a streamlined analysis environment that implements many features which strongly simplify studies dealing with protein sequences and structures and improve productivity. PAT is able to read and write data in many bioinformatics formats and to create any desired pipeline by seamlessly sending the output of a tool to the input of another tool. PAT can retrieve protein entries from identifier-based queries by using pre-computed database indexes. Users can easily formulate complex queries combining different analysis tools with few mouse clicks, or via a dedicated macro language, and a web session manager provides direct access to any temporary file generated during the user session. PAT is freely accessible on the Internet at http://pat.cbs.cnrs.fr.

Computational Biology↗
PubMed2005

New binding specificities derived from Min-23, a small cystine-stabilized peptidic scaffold.

The randomization of both internal and surface residues in small protein domains followed by selection from a display library is emerging as a powerful strategy to obtain novel binding specificities. Small and stable scaffold motifs observed in disulfide-rich proteins are attractive because they are small, stable, and accessible to chemical synthesis. The elementary structural motif found in the squash trypsin inhibitor EETI-II (Ecballium elaterium trypsin inhibitor) is the cystine stabilized beta-sheet (CSB) motif, found in nearly 50% of all known small disulfide-rich protein families. We have used Min-23, a short 23-residue peptide containing the CSB motif and shown to be a stable autonomous folding unit and one of the smallest scaffolds described to date, as a scaffold for selection of new binding ligands. We demonstrate that the core CSB motif in Min-23 is permissive to loop insertion, using peptide epitopes from hemagglutinin (HA) and Gla-protein (E). A phage library of more than 10(8) different clones has been constructed by insertion of a randomized sequence on a beta-turn of the Min-23 peptide. The selection of this library on a variety of 7 different targets allowed the isolation of 21 new specific binders, confirming the potential of Min-23 as a scaffold for the development of new ligands. The derived library is able to provide a wide range of novel compounds with possible applications in various biological and pharmaceutical areas.

Amino Acid Motifs↗
PubMed2005

Acid-triggered membrane insertion of Pseudomonas exotoxin A involves an original mechanism based on pH-regulated tryptophan exposure.

Exposure to low endosomal pH during internalization of Pseudomonas exotoxin A (PE) triggers membrane insertion of its translocation domain. This process is a prerequisite for PE translocation to the cytosol where it inactivates protein synthesis. Although hydrophobic helices enable membrane insertion of related bacterial toxins such as diphtheria toxin, the PE translocation domain is devoid of hydrophobic stretches and the structural features triggering acid-induced membrane insertion of PE are not known. Here we have identified a molecular device that enables PE membrane insertion. This process is promoted by exposure of a key tryptophan residue. At neutral pH, this Trp is buried in a hydrophobic pocket closed by the smallest alpha-helix of the translocation domain. Upon acidification, protonation of the Asp that is the N-cap residue of the helix leads to its destabilization, enabling Trp side chain insertion into the endosome membrane. This tryptophan-based membrane insertion system is surprisingly similar to the membrane-anchoring mechanism of human annexin-V and could be used by other proteins as well.

Animals↗
PubMed2005

EvDTree: structure-dependent substitution profiles based on decision tree classification of 3D environments.

BACKGROUND: Structure-dependent substitution matrices increase the accuracy of sequence alignments when the 3D structure of one sequence is known, and are successful e.g. in fold recognition. We propose a new automated method, EvDTree, based on a decision tree algorithm, for automatic derivation of amino acid substitution probabilities from a set of sequence-structure alignments. The main advantage over other approaches is an unbiased automatic selection of the most informative structural descriptors and associated values or thresholds. This feature allows automatic derivation of structure-dependent substitution scores for any specific set of structures, without the need to empirically determine best descriptors and parameters. RESULTS: Decision trees for residue substitutions were constructed for each residue type from sequence-structure alignments extracted from the HOMSTRAD database. For each tree cluster, environment-dependent substitution profiles were derived. The resulting structure-dependent substitution scores were assessed using a criterion based on the mean ranking of observed substitution among all possible substitutions and in sequence-structure alignments. The automatically built EvDTree substitution scores provide significantly better results than conventional matrices and similar or slightly better results than other structure-dependent matrices. EvDTree has been applied to small disulfide-rich proteins as a test case to automatically derive specific substitutions scores providing better results than non-specific substitution scores. Analyses of the decision tree classifications provide useful information on the relative importance of different structural descriptors. CONCLUSIONS: We propose a fully automatic method for the classification of structural environments and inference of structure-dependent substitution profiles. We show that this approach is more accurate than existing methods for various applications. The easy adaptation of EvDTree to any specific data set opens the way for class-specific structure-dependent substitution scores which can be used in threading-based remote homology searches.

Alanine↗
PubMed2005

Spontaneous dissection of the extracranial vertebral artery: indications and long-term outcome of surgical treatment.

Spontaneous dissection of the vertebral artery (VA) is usually managed medically. The objective of this report was to describe 10 patients treated surgically for spontaneous dissection of the VA. Seven men and three women with a mean age of 52.5 +/- 11.3 years were treated between December 1978 and January 2001. In eight cases the presenting symptom was neck pain. Transient ischemic attack or completed stroke in the vertebrobasilar distribution followed in nine cases. In the remaining case, symptoms resulted from irritation of the superior roots of the brachial plexus. Dissection was located in one segment of the VA in seven cases and two contiguous segments in three cases. Lesions involved aneurysm in seven cases, tight stenosis in two, and occlusion in one. The decision to perform surgery was made because of either continued symptoms despite maximal anticoagulation therapy or the presence of an aneurysm causing recurrent thromboembolism or threatening rupture. In eight cases the revascularization procedure consisted of bypass from the carotid artery to the distal VA. In the remaining two cases revascularization was achieved by transposition of the VA directly onto the common or internal carotid artery. Postoperative recovery was uneventful in all cases. No further neurological events were observed in any patient at a mean follow-up of 96.9 +/- 66 months (range, 12-216 months). Long-term resolution of vertebrobasilar symptoms was achieved in all cases, including one patient whose bypass occluded at 6 months. From these results we conclude that surgical treatment is the method of choice for spontaneous dissection of the extracranial VA associated with continued vertebrobasilar symptoms despite maximal medical therapy or with an expanding aneurysm. The most useful technique is bypass to the distal VA. Morbidity is low and long-term outcome is excellent.

Adult↗
PubMed2005

Use of the ascending aorta as bypass inflow for treatment of chronic intestinal ischemia.

PURPOSE: Surgical revascularization of intestinal arteries is an effective long-term treatment for chronic intestinal ischemia (CII) regardless of the technique used. Conventional antegrade or retrograde bypass techniques are the most common modalities for extensive lesions that cannot be treated by endarterectomy or transposition. In this report, we describe our experience with an antegrade bypass technique from the ascending aorta in patients with no other available inflow. METHODS: From April 1990 to May 2004, we performed antegrade bypass from the ascending aorta to the celiac artery, superior mesenteric artery (SMA), or both in five patients. These cases accounted for 2.4% of the 211 patients who underwent surgery on intestinal arteries during the study period. RESULTS: Four patients presented with symptomatic CII, and one patient had no intestinal ischemic symptoms. The underlying disease was Takayasu disease in two cases, Erdheim-Chester disease in one case, chronic aortic dissection in one case, and atherosclerosis in one case. Two patients had already undergone an unsuccessful revascularization attempt with another technique. Bypass was performed alone in three cases in association with revascularization of the ascending aorta, aortic arch, and proximal descending thoracic aorta in one case and in association with revascularization of the ascending aorta and proximal aortic arch and renal autotransplantation in one case. Recovery was uneventful in all cases. One venous graft occluded because of technical defects and required reoperation for prosthetic graft replacement on the 10th postoperative day. Symptoms of CII resolved in all cases. Four months after the procedure, one patient underwent dilatation of an asymptomatic stenosis of the SMA distal to the bypass. During the 50th month after the procedure, a new re-stenosis of the SMA appeared. Left untreated, this stenosis led to asymptomatic occlusion of the mesenteric segment of a sequential aortoceliomesenteric bypass 13 months later. This aortoceliac bypass and the other four bypasses were patent after 4, 31, 46, 52, and 120 months of follow-up. CONCLUSION: Antegrade intestinal artery bypass from the ascending aorta is an effective alternative for patients who have no other available inflow for conventional antegrade or retrograde bypass and for patients in whom major technical difficulties are likely after multiple exposures of the thoracoabdominal aorta. Although indications are uncommon, antegrade intestinal artery bypass can provide durable revascularization of the intestine.

Adult↗
PubMed2005

Open repair of chronic post-traumatic aneurysms of the aortic isthmus: the value of direct aortoaortic anastomosis.

PURPOSE: This report presents our experience with open repair of post-traumatic aneurysms of the aortic isthmus using recent surgical techniques, including distal aortic perfusion and the preferential use of direct aortoaortic anastomosis without interposition of prosthetic material. METHODS: From 1990 to 2004, the senior author (EK) patients (21 men; mean age, 40.3 years) who presented with post-traumatic aneurysms of the aortic isthmus were treated operatively, either with (20 patients) or without (3 patients) distal aortic perfusion, or endovascularly with a stent graft (3 patients). In 15 (75 %) of the 20 patients treated with distal aortic perfusion, the technique consisted of resection followed by direct aortoaortic anastomosis. Eight patients, including the three patients treated with simple clamping, had prosthetic replacement. RESULTS: No postoperative deaths or permanent spinal cord complications occurred. One patient required reoperation to control hemorrhage. Aortography or computed tomography angiography was performed on 12 of the 15 patients treated by direct aortoaortic anastomosis, with a mean follow-up of 58.7 +/- 8.9 months. No morphologic abnormality was found. CONCLUSION: This study shows that low-risk patients with a chronic post-traumatic aneurysm of the aortic isthmus can be successfully treated with excellent long-term results by resection and direct aortoaortic anastomosis without prosthetic interposition. In our opinion, endovascular repair should only be used in patients who present with absolute contraindications for open surgical repair.

Accidents, Traffic↗
PubMed2004

High-resolution X-ray structure of the unexpectedly stable dimer of the [Lys(-2)-Arg(-1)-des(17-21)]endothelin-1 peptide.

Previous structural studies on the [Lys((-2))-Arg((-1))]endothelin-1 peptide (KR-ET-1), 540-fold less potent than ET-1, strongly suggested the presence of an intramolecular Arg(-1)-Asp(8) (R(-1)-D(8)) salt bridge that was also observed in the shorter [Lys((-2))-Arg((-1))-des(17-21)]endothelin-1 derivative (KR-CSH-ET). In addition, for these two analogues, we have shown that the Lys-Arg dipeptide, which belongs to the prosequence, significantly improves the formation of the native disulfide bonds (>or=96% instead of approximately 70% for ET-1). In contrast to what was inferred from NMR data, molecular dynamics simulations suggested that such an intramolecular salt bridge would be unstable. The KR-CSH-ET peptide has now been crystallized at pH 5.0 and its high-resolution structure determined ab initio at 1.13 A using direct methods. Unexpectedly, KR-CSH-ET was shown to be a head-to-tail symmetric dimer, and the overall interface involves two intermolecular R(-1)-D(8) salt bridges, a two-stranded antiparallel beta-sheet, and hydrophobic contacts. Molecular dynamics simulations carried out on this dimer clearly showed that the two intermolecular salt bridges were in this case very stable. Sedimentation equilibrium experiments unambiguously confirmed that KR-ET-1 and KR-CSH-ET also exist as dimers in solution at pH 5.0. On the basis of the new dimeric structure, previous NMR data were reinterpreted. Structure calculations were performed using 484 intramolecular and 38 intermolecular NMR-derived constraints. The solution and the X-ray structures of the dimer are very similar (mean rmsd of 0.85 A). Since the KR dipeptide at the N-terminus of KR-CSH-ET is present in the prosequence, it can be hypothesized that similar intermolecular salt bridges could be involved in the in vivo formation of the native disulfide bonds of ET-1. Therefore, it appears to be likely that the prosequence does assist the ET-1 folding in a chaperone-like manner before successive cleavages that yield the bioactive ET-1 hormone.

Amino Acid Sequence↗
PubMed2004

Descending thoracic and thoracoabdominal aortic aneurysm in patients with Takayasu's disease.

From June 1974 to December 2001 we performed operative treatment on 33 patients with descending thoracic or thoracoabdominal aortic aneurysm in association with Takayasu disease. There were 25 men and 8 women with a mean age of 40.2A years (range 16-64A years). Nineteen patients came from North Africa, 6 were from France, and 8 were from various locations in the world. The revealing symptom was hypertension in 12 cases, thoracic or abdominal pain in 7, isolated inflammatory syndrome in 5, neurologic or ocular manifestations in 3, rupture in 3, and embolization to the lower extremity in 1. In the remaining two cases discovery was coincidental. The aneurysm was confined to the thoracic aorta in 10 cases and involved both the thoracic and abdominal aorta in 23 cases. There were 8 type I, 6 type II, 4 type III, and 5 type IV aneurysms according to Crawford's classification. Two patients had undergone previous repair of the thoracoabdominal aorta. Four patients required first-stage treatment of a renal artery lesion to control hypertension. Six patients had associated aneurysms of the proximal aorta, including five treated via the distal elephant trunk technique in first-stage procedures. Aneurysm repair consisted of prosthetic replacement of the thoracoabdominal aorta in 31 cases, exclusion bypass in 1 case, and stent graft placement in 1 case. The procedure was performed with cross-clamping alone in 13 cases, distal perfusion in 17 cases, and deep hypothermic circulatory arrest in 3 cases. Twenty patients (61%) had associated renal and/or intestinal artery lesions that were treated during the same procedure as that for the thoracoabdominal aorta in 19 patients (58%). A total of 24 procedures were performed on renal arteries (17 revascularizations, 7 nephrectomies). Associated supraaortic trunks lesions were present in 15 patients (45%) and were treated in 12 patients, including 8 in first-stage procedures prior to thoracoabdominal aortic aneurysm repair. Three patients died of multiple organ failure, after reoperation in two cases and infection in one case involving prior long-term corticosteroid therapy. Three patients developed paraplegia, including one who had undergone emergency treatment following rupture. Two patients required reoperation, for hematoma in one case and bowel necrosis in one. Four patients developed respiratory complications requiring artificial ventilation for more than 48 hr. During follow-up, two patients died from complications after repair of the proximal aorta and one patient required nephrectomy. Despite the extent of aneurysmal lesions and high frequency of association with visceral and supraaortic vessel lesions, the outcome of surgery in patients presenting with descending thoracic or thoracoabdominal aortic aneurysm in association with Takayasu disease was satisfactory.

Adult↗
PubMed2004

The KNOTTIN website and database: a new information system dedicated to the knottin scaffold.

The KNOTTIN website and database organize information about knottins or inhibitor cystine knots, small disulfide-rich proteins with a knotted topology. Thanks to their small size and high stability, knottins provide appealing scaffolds for protein engineering and drug design. Static pages present the main historical and recent results about knottin discoveries, sequences, structures, folding, functions, applications and bibliography. Database searches provide dynamically generated tabular reports or sequence alignments for knottin three-dimensional structures or sequences. BLAST/HMM searches are also available. A simple nomenclature, based on loop lengths between cysteines, is proposed and is complemented by a uniform numbering scheme. This standardization is applied to all knottin structures in the database, facilitating comparisons. Renumbered and structurally fitted knottin PDB files are available for download. The standardized numbering is used for automatic drawing of two-dimensional Colliers de Perles. The KNOTTIN website and database are available at http://knottin.cbs.cnrs.fr and http://knottin.com.

Amino Acid Motifs↗
PubMed2004

Allograft replacement for infrarenal aortic graft infection: early and late results in 179 patients.

OBJECTIVES: We evaluated early and late results of allograft replacement to treat infrarenal aortic graft infection in a large number of patients and compared the results in patients who received fresh allografts versus patients who received cryopreserved allografts. METHODS: From 1988 to 2002 we operated on 179 consecutive patients (mean age, 64.6 +/- 9.0 years; 88.8% men). One hundred twenty-five patients (69.8%) had primary graft infections, and 54 patients (30.2%) had secondary aortoenteric fistulas (AEFs). Fresh allografts were used in 111 patients (62.0%) until 1996, and cryopreserved allografts were used in 68 patients (38.0%) thereafter. RESULTS: Early postoperative mortality was 20.1% (36 patients), including four (2.2%) allograft-related deaths from rupture of the allograft (recurrent AEF, n = 3), all in patients with fresh allografts. Thirty-two deaths were not allograft related. Significant risk factors for early mortality were septic shock (P <.001), presence of AEF (P =.04), emergency operation (P =.003), emergency allograft replacement (P =.0075), surgical complication (P =.003) or medical complication (P <.0001), and need for repeat operation (P =.04). There were five (2.8%) nonlethal allograft complications (rupture, n = 2; thromboses, which were successfully treated at repeat operation, n = 2; and amputation, n = 1), all in patients with fresh allografts. Four patients (2.2%) were lost to follow-up. Mean follow-up was 46.0 +/- 42.1 months (range, 1-148 months). Late mortality was 25.9% (37 patients). There were three (2.1%) allograft-related late deaths from rupture of the allograft, at 9, 10, and 27 months, respectively, all in patients with fresh allografts. Actuarial survival was 73.2% +/- 6.8% at 1 year, 55.0% +/- 8.8% at 5 years, and 49.4% +/- 9.6% at 7 years. Late nonlethal aortic events occurred in 10 patients (7.2%; occlusion, n = 4; dilatation < 4 cm, n = 5; aneurysm, n = 1), at a mean of 28.3 +/- 28.2 months, all but two in patients with fresh allografts. The only significant risk factor for late aortic events was use of an allograft obtained from the descending thoracic aorta (P =.03). Actuarial freedom from late aortic events was 96.6% +/- 3.4% at 1 year, 89.3% +/- 6.6% at 3 years, and 89.3% +/- 6.6% at 5 years. There were 63 late, mostly occlusive, iliofemoral events, which occurred at a mean of 34.9 +/- 33.7 months in 38 patients (26.6%), 28 of whom (73.7%) had received fresh allografts. The only significant risk factor for late iliofemoral events was use of fresh allografts versus cryopreserved allografts (P =.03). Actuarial freedom from late iliofemoral events was 84.6% +/- 7.0% at 1 year, 72.5% +/- 9.0% at 3 years, and 66.4% +/- 10.2% at 5 years. CONCLUSIONS: Early and long-term results of allograft replacement are at least similar to those of other methods to manage infrarenal aortic graft infections. Rare specific complications include early or late allograft rupture and late aortic dilatation. The more frequent late iliofemoral complications may be easily managed through the groin. These complications are significantly reduced by using cryopreserved allografts rather than fresh allografts and by not using allografts obtained from the descending thoracic aorta.

Aorta, Abdominal↗
PubMed2004

Sequential development of perinuclear ANCA-associated vasculitis and anti-glomerular basement membrane glomerulonephritis.

A 75-year-old man suffered from perinuclear antineutrophil cytoplasm antibody (p-ANCA)-associated vasculitis with mild renal involvement. Three years later, he suddenly experienced an anuric acute renal failure due to anti-glomerular basement membrane (GBM) disease. Antibodies to myeloperoxydase were continuously present at a high titer in the patient's serum while serum anti-GBM antibodies were only detected at the time of the acute renal failure. A substantial proportion of patients with anti-GBM glomerulonephritis simultaneously display ANCAs whose pathogenic role is not clear. In our case, ANCAs were supposed to be of pathogenic importance because they may have uncovered the Goodpasture antigen. This case report lends further support to the concept that p-ANCA vasculitis may trigger anti-GBM disease.

Aged↗
PubMed2004

Squash inhibitors: from structural motifs to macrocyclic knottins.

In this article, we will first introduce the squash inhibitor, a well established family of highly potent canonical serine proteinase inhibitors isolated from Cucurbitaceae. The squash inhibitors were among the first discovered proteins with the typical knottin fold shared by numerous peptides extracted from plants, animals and fungi. Knottins contain three knotted disulfide bridges, two of them arranged as a Cystine-Stabilized Beta-sheet motif. In contrast to cyclotides for which no natural linear homolog is known, most squash inhibitors are linear. However, Momordica cochinchinensis Trypsin Inhibitor-I and (MCoTI-I and -II), 34-residue squash inhibitors isolated from seeds of a common Cucurbitaceae from Vietnam, were recently shown to be macrocyclic. In these circular squash inhibitors, a short peptide linker connects residues that correspond to the N- and C-termini in homologous linear squash inhibitors. In this review we present the isolation, characterization, chemical synthesis, and activity of these macrocyclic knottins. The solution structure of MCoTI-II will be compared with topologically similar cyclotides, homologous linear squash inhibitors and other knottins, and potential applications of such scaffolds will be discussed.

Amino Acid Sequence↗
PubMed2003

Primary tumors of the thoracoabdominal aorta: surgical treatment of 5 patients and review of the literature.

The objectives of this study were to describe five cases involving primary tumors of the thoracoabdominal aorta and to review the pertinent literature. Between April 1990 and April 2000, we performed surgery on five patients with primary tumors of the aorta (PTA). There were three men and two women ranging in age from 37 to 65 years (mean, 49.8 years). The presenting manifestations were renovascular hypertension in four cases, including three associated with abdominal angina and lower extremity embolism in one case. In all patients aortograms identified atherosclerotic-like occlusive lesions in the thoracoabdominal aorta extending to the descending thoracic aorta in three cases, visceral arteries in four cases, and infrarenal aorta in one case. Preoperative histological diagnosis of PTA was achieved in two patients following open repair with placement of an aortoaortic graft in one case and peripheral embolectomy in one case. In two cases, diagnosis of PTA was strongly suspected before or during the procedure. In the remaining case, diagnosis was not achieved until the definitive histological report. In two patients surgical treatment was carried out with curative intent (aortic resection with graft replacement). In two cases surgical treatment was incomplete (endarterectomy of the aorta and visceral arteries). In the remaining case surgical treatment was purely palliative (aortic and superior mesenteric artery bypass). Histological findings demonstrated intimal-type sarcoma in two cases, leiomyosarcoma in one case, and angiosarcoma in one case. In the remaining case, histological analysis was unfeasible for technical reasons. One patient died due to massive cerebral embolism 2 days after surgical treatment involving revascularization of the aortic arch carried out with hypothermic circulatory arrest. One patient developed secondary paraplegia. All four patients who survived the immediate postoperative period died of tumor-related complications and cachexia at 5, 7, 16, and 24 months after the initial surgical procedure. The results of this small series as well as those of 130 previously reported cases confirm the extremely dismal prognosis of PTA. Mean overall survival for patients presenting PTA was less than 16 months. Survival at 5 years was 8%. Survival rates appear to be higher after surgical treatment and were significantly improved by adjuvant chemotherapy. The main factors correlated with poor prognosis were intimal type, involvement of the ascending aorta, aortic arch, or visceral aorta, and incomplete resection.

Adult↗