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Biomedical subjects

P Desgranges

Publications and source records attributed to P Desgranges.

61 records · Page 4Linked to original sources

Mitogenic and in vitro angiogenic activity of human recombinant heparin affin regulatory peptide.

We have previously described the purification of a heparin binding growth factor from adult bovine brain named heparin affin regulatory peptide (HARP), which was identical to an uterus derived growth factor named pleiotrophin and to a developmentally regulated neurite promoting factor named heparin-binding growth associated molecule. However, for yet unclear reasons, the mitogenic activity of this purified polypeptide following isolation from animal tissue extracts is a subject of controversy, due to conflicting and irreproducible data when produced by recombinant DNA technologies in E. coli or insect cells. The purified protein was inactive in mitogenic assays but the natural molecule was active in assay of neurite outgrowth. In order to clarify these conflicting results and to obtain a recombinant protein free from other contaminating heparin-binding growth factors, we have cloned human cDNA encoding human HARP, engineered its expression in NIH 3T3 cells and characterised the resulting recombinant polypeptide. Purified recombinant HARP displayed mitogenic activity for capillary endothelial cells with half-maximal stimulation at approximately 1 ng/ml (55 pM) and induced angiogenesis in an in vitro model. Interestingly, while the NH2 terminal sequence of tissue purified HARP was NH2-GKKEKPEKK, the NH2 terminal sequence of the biologically active recombinant protein was NH2-AEAGKKEKPEKK, corresponding to a three amino acid extended form.

3T3 Cells↗

Mesoglycan and sulodexide act as stabilizers and protectors of fibroblast growth factors (FGFs).

Heparin and heparan sulfate proteoglycans (HSPGs) stabilize FGFs which belong to heparin-binding growth factors (HBGFs) on active conformation. They also strongly potentiate their mitogenic activity on many cell types, and protect them against thermal denaturation and enzymatic degradation. In the present work we have tested two heparin-like substances named mesoglycan and sulodexide obtained from bovine intestinal mucosal extracts. These products are used as heparin, in various of therapeutic fields such as atherosclerosis or antithrombotic therapy. The compositions of mesoglycan and sulodexide are partially known and include chondroitin, dermatan and heparan sulfate. We have shown that mesoglycan and sulodexide potentiated the mitogenic activity of FGF1 and FGF2. The magnitude of this effect was identical with that of heparin used as a control substance but at double concentration. Mesoglycan and sulodexide also exerted stabilizing and protective effects on FGFs for heat denaturation and enzymatic degradation. The suppression of the protective properties after heparinase treatment of mesoglycan and sulodexide indirectly demonstrated the presence of heparan sulfate which was shown to represent about 60% of the commercial products.

Animals↗

Extracellular matrix covered biomaterials for human endothelial cell growth.

The aim of this study is to optimize conditions for growing endothelial cells on vascular biomaterials. Bovine cornea endothelial cells (BCEC), stimulated by basic Fibroblast Growth Factor (bFGF) secrete an extracellular matrix (ECM) similar to the Descemet membrane produced in vivo by these cells. This ECM, obtained by removing BCEC with an hypotonic shock can be used as a substratum for other endothelial cell growth. Human endothelial cells (HEC) were purified from omentum that was digested with a solution of collagenase-dispase, then filtered through nylon meshes. The cells were further purified by centrifugation onto a Percoll gradient. A comparative study on the attachment and growth of HEC on various coatings (laminin, poly-L-lysine, fibronectin or ECM) indicates that ECM is the most performing substratum. The quality of this endothelium was confirmed by the presence of factor VIII, and MHC class I and the absence of class II antigens.

Animals↗

[Heart surgery and human immunodeficiency virus].

The authors report their experience of cardiac surgery in 9 carriers of the human immunodeficiency virus (HIV). Eight HIV seropositive patients underwent surgery under cardiopulmonary bypass for valve repair or replacement. Eight patients were asymptomatic with respect to their viral infection: one patient had generalised lymphadenopathy. The hospital mortality was 1/9 (11.1%). There was no infectious morbidity. Five patients are alive with an average follow-up of 29.6 months and in NYHA Stages I or II. One patient deteriorated and presented symptoms of an AIDS-related complex. These results suggest that if the operative indications are justified, cardiac surgery under cardiopulmonary bypass may be performed in asymptomatic HIV seropositive patients.

AIDS-Related Complex↗

Management of infected vascular prostheses. The vascular homograft revisited.

Treatment of infected aortic femoral grafts is difficult and controversial. We describe the case of a patient who presented for recurrent infections of an aorto-bifemoral prosthesis. An arterial homograft was used to replace the Dacron prosthesis. One year later, the patient is free of symptoms and is doing well. Although early experiences with long-term use of homografts showed late degeneration of the grafts, 2 points should now be raised in favor of homograft use: new techniques of fresh antibiotic storage of homografts appear to have improved durability; and if replacement of a homograft ever becomes necessary, implantation of a Dacron prosthesis could likely be performed in an aseptic environment. While the use of homografts may constitute a reasonable alternative for treating patients with infected vascular grafts, firm conclusions cannot be drawn until we have seen larger series of patients and longer follow-up periods than those few reported to date.

Journal Article↗

[Treatment of type A aortic dissection by exclusive glueing].

From 1984 to 1990, 24 patients suffering from type A aortic dissection were treated by directly suturing the entry orifice of the dissection and glueing (gelatin-resorcin-formaldehyde glue) the dissected aortic tunicae, without any prosthetic replacement. Associated aortic insufficiency in 21 patients was treated by valve replacement (8 patients) or plasty (8 patients). Deep hypothermia with circulatory arrest was required in 13 patients, whose aortic arch was involved by the dissection. All patients survived the operation. All these patients were followed up from 6 to 60 months. All were controlled with Doppler echography. In addition, 21 of them were examined with angiography, 17 with CT and 5 with MRI. 21 patients had an ascending aorta and an apparently normal aortic arch. Limited dissection of the descending aorta, requiring no second surgery, was noted in 2 patients. Persisting dissection of the descending aorta was present in 13 patients. Valve replacement was necessary 18 months later in 1 patient. Heart transplantation was necessary 14 months later in a patient suffering from associated cardiomyopathy. These results demonstrate that aortic glueing is effective and safe in the middle term for the treatment of aortic dissection.

Adult↗

Aortic stents covering the renal arteries ostia: an animal study.

PURPOSE: To evaluate the consequences of placing an aortic stent over the renal arteries. MATERIALS AND METHODS: The renal ostia of 11 pigs were covered by Strecker stents placed in the aorta. At 1 month, the degree of renal ostial stenosis was determined by means of angiography and gross pathologic and histologic examination. Any reduction in area of the renal ostia was considered significant. Preprocedure and 1-month serum creatinine levels were also examined. RESULTS: One stent migrated and was excluded from the study. There was one angiographic failure and, among the remaining 18 renal arteries evaluated, one was occluded, six were stenosed, and 11 were patent. Of the 10 samples available for pathologic examination, one was excluded from study because one stent was not fully deployed. A neointima was covering the struts crossing or encircling the renal arteries ostia with a mean area coverage of 43% +/- 30% (range, 0-84%). Serum creatinine levels rose from 71.1 mumol/L +/- 7.1 preoperatively to 94.2 mumol/L +/- 6.7 postoperatively (P < .01). CONCLUSION: An aortic stent placed over the renal arteries in pigs may compromise renal perfusion in the long-term because neointima tends to fill the spaces between the struts.

Angioplasty↗