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Biomedical subjects

I Martin

Publications and source records attributed to I Martin.

At least 109 records · Page 6Linked to original sources
PubMed1999

Frontiers in tissue engineering. In vitro modulation of chondrogenesis.

Cartilage tissue engineering can provide functional cartilaginous constructs that can be used for controlled in vitro studies of chondrogenesis and potentially for in vivo articular cartilage repair. Ideally, engineered cartilage should be indistinguishable from native articular cartilage with respect to zonal organization, biochemical composition, and mechanical properties. In the model system presented here, chondrogenic cells are expanded in vitro as required, seeded onto three-dimensional polymeric scaffolds, and cultured in bioreactor vessels. During the course of in vitro cultivation, construct cellularity plateaus at a physiologic level, fractions of glycosaminoglycan and Type II collagen increase progressively, and the scaffold biodegrades. Construct structure (composition, morphology) and function (biosynthetic activity, mechanical properties) depend on cultivation conditions. This paper reviews recent studies of in vitro modulation of chondrogenesis by: (1) cell seeding density and source; (2) the tissue regeneration template; (3) biochemical regulatory signals; (4) mixing, mass transport and hydrodynamic forces; and (5) cultivation time. Key requirements and some of the critical research needs for successful cartilage tissue engineering are discussed.

Animals↗
PubMed1998

Structural properties of the putative fusion peptide of fertilin, a protein active in sperm-egg fusion, upon interaction with the lipid bilayer.

We recently demonstrated that a peptide representing the putative fusion domain of fertilin, a surface membrane protein of sperm involved in sperm-egg fusion, induces fusion of large unilamellar vesicles containing negatively charged lipids [Martin, I., and Ruysschaert, J. M. (1997) FEBS Lett. 405, 351-355]. In the present work, we demonstrate that increasing the concentration in negatively charged lipids strongly enhances the binding of the fertilin fusion peptide to the membrane, suggesting that electrostatic attractions play a crucial role in the binding process. While no significant change of the secondary structure content is observed by increasing the amounts of negatively charged lipids in the bilayer, the orientation of the alpha-helix changes from a parallel to an oblique orientation in the membrane. This topological change is confirmed by amide II hydrogen/deuterium exchange measurements that monitor the accessibility of the peptide to the water medium. Differential scanning calorimetry data also suggest that the fertilin fusion peptide lowers the bilayer to hexagonal phase transition temperature of model membranes composed of mixtures of dipalmitoleoylphosphatidylethanolamine and 1-palmitoyl-2-oleoylphosphatidylserine and therefore promotes negative curvature in lipid vesicles. A comparison of the biophysical properties and the membrane-perturbing activities of fertilin and of viral fusion peptides is discussed in terms of sperm-egg fusion and virus cell fusion.

ADAM Proteins↗
PubMed1998

Lipophosphoglycan of Leishmania donovani inhibits lipid vesicle fusion induced by the N-terminal extremity of viral fusogenic simian immunodeficiency virus protein.

Lipophosphoglycan (LPG), the major glycoconjugate of Leishmania parasites, was recently shown to be a potent inhibitor of viral infection. The mechanism by which this natural membrane amphiphile compound inhibits membrane fusion was investigated in this study using a simple model membrane system and a synthetic peptide corresponding to the fusion peptide of simian immunodeficiency virus (SIV). At low concentration (< 10 microM), LPG inhibits SIV-induced lipid mixing of large unilamellar vesicles composed of an equimolar mixture of egg phosphatidylcholine and egg phosphatidylethanolamine. Importantly, this inhibition was observed regardless of which LPG was inserted in the inner monolayer, the outer monolayer or both sides of the membrane, suggesting that the inner monolayer plays a determining role in membrane fusion. Fourier transform infrared spectroscopy revealed that LPG induced a conformational change of SIV fusion peptide without affecting its capacity to interact with the lipid membrane. This structural change was shown not to depend on the LPG localization and was observed even when LPG was exclusively associated to the inner lipid membrane.

Animals↗
PubMed1998

Chondrogenesis in a cell-polymer-bioreactor system.

Chondrogenesis was studied under controlled in vitro conditions using a cell-polymer-bioreactor system. Bovine calf articular chondrocytes were seeded onto biodegradable polymer scaffolds and cultured in rotating bioreactor vessels. Concomitant increases in the amounts of glycosaminoglycan (GAG) and type II collagen resulted in cell-polymer constructs with continuous cartilaginous matrix over their entire cross sections (6.7 mm diameter x 5 mm thick) after 40 days of cultivation. As compared to natural calf cartilage, constructs had comparable cellularities, 68% as much GAG and 33% as much type II collagen per gram wet weight. The progression of chondrogenesis in chondrocyte-polymer constructs was similar to that suggested previously for precursor cells in vitro and developing limbs in vivo. In particular, the polymer scaffold provided a three-dimensional structure that could be seeded with chondrocytes at high cell densities in order to establish cell-to-cell contacts and initiate cartilage tissue development, whereas the bioreactor vessel provided a permissive microenvironment for chondrogenesis. This work demonstrates the promise of using tissue engineered constructs for in vitro studies of cell interactions and differentiation.

Animals↗
PubMed1998

Oxidative damage, plasma antioxidant capacity, and glucemic control in elderly NIDDM patients.

A study of oxidative damage was made in elderly noninsulin-dependent diabetes mellitus (NIDDM) patients. A statistically significant increase in glucose and fructosamine was found in fasting NIDDM patients, as well as an increase in the oxidation induced by tert-butyl hydroperoxide. The Total Reactive Antioxidant Potential (TRAP) of the plasma was much reduced (p < .02) and the uricemia was unchanged. The erythrocytes of diabetic patients show greater basal oxidation products (p < .05), and the susceptibility of the diabetic erythrocytes to oxidation injury was also shown to increase in the oxidation induced by t-BOOH (p < .05). Linear regression studies showed that TRAP was associated directly with uric acid (p < .05) and inversely with fructosamine and with glucose (p < .03 and p < .05 respectively) in patients with NIDDM, but not in the controls. The levels of fructosamine were found to be related to the basal damage of the red blood cells (direct correlation, p < .001). This study suggest an useful approach to diabetic oxidative stress for clinical settings.

Adult↗
PubMed1998

Membrane fusion induced by 11-mer anionic and cationic peptides: a structure-function study.

We recently demonstrated that an amphipathic net-negatively charged peptide consisting of 11 amino acids (WAE 11) strongly promotes fusion of large unilamellar liposomes (LUV) when anchored to a liposomal membrane [Pecheur, E. I., Hoekstra, D., Sainte-Marie, J., Maurin, L., Bienvenue, A., and Philippot, J. R. (1997) Biochemistry 36, 3773-3781]. To elucidate a potential relationship between peptide structure and its fusogenic properties and to test the hypothesis that specific structural motifs are a prerequisite for WAE-induced fusion, three 11-mer WAE-peptide analogues (WAK, WAEPro, and WAS) were synthesized and investigated for their structure and fusion activity. Structural analysis of the synthetic peptides by infrared attenuated total reflection spectroscopy reveals a distinct propensity of each peptide toward a helical structure after their anchorage to a liposomal surface, emphasizing the importance of anchorage on conveying a secondary structure, thereby conferring fusogenicity to these peptides. However, whereas WAE and WAK peptides displayed an essentially nonleaky fusion process, WAS- and WAEPro-induced fusion was accompanied by substantial leakage. It appears that peptide helicity as such is not a sufficient condition to convey optimal fusion properties to these 11-mer peptides. Studies of changes in the intrinsic Trp fluorescence and iodide quenching experiments were carried out and revealed the absence of migration of the Trp residue of WAS and WAEPro to a hydrophobic environment, upon their interaction with the target membranes. These results do not support the penetration of both peptides as their mode of membrane interaction and destabilization but rather suggest their folding along the vesicle surface, posing them as surface-seeking helixes. This is in striking contrast to the behavior observed for WAE and WAK, for which at least partial penetration of the Trp residue was demonstrated. These results indicate that subtle differences in the primary sequence of a fusogenic peptide could induce dramatic changes in the way the peptide interacts with a bilayer, culminating in equally drastic changes in their functional properties. The data also reveal a certain degree of sequence specificity in WAE-induced fusion.

Amino Acid Sequence↗
PubMed1998

Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases.

We have evaluated the performance of a new analyzer using high shear stress, the PFA-100 (Platelet Function Analyzer, Dade International, Massy, France), for screening of patients with von Willebrand disease (vWD). Whole citrated blood is aspirated through a capillary to the central aperture of a membrane coated with collagen and with a platelet agonist (either epinephrine or adenosine diphosphate [ADP]). The time required to obtain occlusion of the aperture by a platelet plug is defined as the closure time (CT). We studied 60 patients with different types of vWD and 96 normal subjects. Fourteen subjects with hemophilia and 15 patients with a platelet disorder were also analyzed. When omitting results from two patients with type 2N, the 58 other patients with type 1, type 2A, type 2B, type 3, or acquired vWD all exhibited an abnormal occlusion with collagen-ADP (sensitivity, 100%) and 56 of 58 had an abnormal CT with collagen-epinephrine (sensitivity, 96.5%). Only two patients with mild type 1 were not detected with collagen-epinephrine. In comparison, the bleeding time (BT) was normal in 20 patients: 17 with type 1, two with type 2A, and one with acquired vWD (sensitivity, 65.5%). The specificity of the PFA-100 was over 95% with both types of cartridges. Thus, the analyzer is well adapted to routine testing, as it has the advantages of simplicity and ease of execution, and demonstrates a high sensitivity, clearly superior to that of BT, for the screening of patients with vWD.

Adolescent↗
PubMed1998

Cardiac surgical mortality: comparison among different additive risk-scoring models in a multicenter sample.

OBJECTIVE: To compare the performance of several risk-scoring models to predict surgical mortality following open heart surgery. DESIGN: A prospective observational study. SETTING: Seven tertiary cardiac centers (3 private and 4 public and teaching hospitals) in Catalonia (Spain). PATIENTS: A consecutive sample of 1287 patients submitted to open heart surgery during a 6 1/2-month period (February 14, 1994, to August 31, 1994). INTERVENTION: None. MAIN OUTCOME MEASURE: Model discrimination capability was assessed with the c-statistic. A chi(2) test to compare observed and predicted mortality rates was used as a measure of model calibration. Performance of centers was evaluated through the standardized mortality ratio and using the center as an indicator variable in a logistic regression model. The agreement among models for individual predictions was tested using weighted K statistics. RESULTS: Models developed in other health care contexts showed, as expected, lower c-statistics and an inappropriate calibration. There were no statistically significant differences among hospitals after adjusting for baseline patients' risk factors with the use of any of the different models. Models also agree in the standardized rank of centers. Weighted K statistics indicated poor agreement among models for individual patient risk prediction. CONCLUSIONS: Models can be a useful tool to compare providers' performance and to give a more in-depth look at the process of care when appropriately customized to the context. Severity-adjusted models can also play a role in supporting the informed and subjective surgeon's assessment, but it is inappropriate to use them for individual predictions.

Cardiac Surgical Procedures↗
PubMed1998

In vitro differentiation of chick embryo bone marrow stromal cells into cartilaginous and bone-like tissues.

Bone marrow stromal cells, progenitor cells involved in repair of bone and cartilage, can potentially provide a source for autologous skeletal tissue engineering. We investigated which factors were required to induce in vitro differentiation of avian bone marrow stromal cells into three-dimensional cartilaginous and bone-like tissues. Bone marrow stromal cells from embryonic chicks were expanded in monolayers, seeded onto biodegradable polyglycolic acid scaffolds, and cultured for 4 weeks in orbitally mixed Petri dishes. Cell-polymer constructs developed an organized extracellular matrix containing glycosaminoglycans and collagen, whereas control bone marrow stromal cell pellet cultures were smaller and consisted predominantly of fibrous tissue. Bone marrow stromal cells expanded with fibroblast growth factor-2 and seeded onto polymer scaffolds formed highly homogeneous three-dimensional tissues that contained cartilage-specific molecular markers and had biochemical compositions comparable with avian epiphyseal cartilage. When cell-polymer constructs were cultured in the presence of beta-glycerophosphate and dexamethasone, the extracellular matrix mineralized and bone-specific proteins were expressed. Our work shows that cell expansion in the presence of fibroblast growth factor-2 and cultivation on a three-dimensional polymer scaffold allows differentiation of chick bone marrow stromal cells into three-dimensional cartilaginous tissues. In the in vitro system studied, the same population could be selectively induced to regenerate either cartilaginous or bone-like tissue.

Animals↗
PubMed1998

Total or subtotal gastrectomy for gastric carcinoma? A study of quality of life.

The aim of this study was to compare quality of life after total gastrectomy (TG) with that after subtotal gastrectomy (STG) for gastric carcinoma. The value of the routine use of TG de principe in the treatment of gastric carcinoma, wherever the tumor may be sited in the stomach, remains controversial. The advocates of TG contend that when it can be performed safely, with relatively low operative mortality and morbidity, it yields better long-term survival than STG. Most surgeons, however, believe that the routine use of TG increases both operative mortality and morbidity and the risk of nutritional deficiency in the long term, without improving survival. TG may also be associated with poorer outcome in terms of quality of life (QOL), but the evidence for this is tenuous. Forty-seven consecutive patients who had undergone potentially curative (R0) gastric resection for carcinoma were studied: 26 had undergone TG and 21 STG. A radical D2 lymph node dissection had been performed in each, and all patients were free from recurrence at the time of the study. QOL was measured before operation and 1, 3, 6, and 12 months after operation by means of five questionnaires to measure functional outcome: the Rotterdam symptom checklist (RSCL), the Troidl index, the hospital anxiety and depression (HAD) scale, activities of daily living score, and Visick grades. Before operation there was no significant difference in QOL between the two groups of patients. At 1 year after operation, however, patients who had undergone STG had a significantly better QOL than patients who had undergone TG: Their median RSCL score was lower (10 versus 19 respectively, p < 0.05), and their Troidl index was higher (11 versus 9 respectively, p < 0.05). The QOL of patients who underwent STG was also significantly better after operation than it had been before operation, whereas the QOL of the TG group was not significantly better after operation than before operation. The QOL of patients was found to be significantly better after STG than after TG for gastric carcinoma. Because operative mortality is greater and long-term survival is no better after TG than after STG, the latter is recommended as the treatment of choice for tumors of the distal stomach.

Activities of Daily Living↗
PubMed1998

A nude mouse model for human bone formation in unloaded conditions.

We describe an experimental model for human bone formation in unloaded conditions. Bone formation has been assessed by implanting in vivo human bone marrow stromal cells (BMSC) on porous hydroxyapatite (HA) bioceramics subcutaneously in nude mice. In this system, human bone formation and remodeling occurs and can be studied in unloaded conditions, i.e., with no influence of muscle tension. Using this model system, we have been also studying the effects of dexamethasone (Dex) in combination with fibroblast growth factor-2 (FGF-2) on the osteogenic potential of human BMSC. A colony-forming unit-fibroblastoid (CFU-F) formed in clonal conditions were significantly larger when Dex/FGF-2 was present in the culture medium. The cell proliferation rate was also increased by the combination Dex/FGF-2 at a higher extent than Dex or FGF-2 alone. BMSC expanded with Dex/FGF-2 displayed alkaline phosphatase levels lower (56%) than Dex expanded cells, but significantly higher than FGF-2 expanded cells. Our results suggest that Dex/FGF-2 expanded BMSC are able to form more bone than BMSC expanded in the presence of FGF-2 alone.

Adult↗
PubMed1998

Structural study of the interaction between the mitochondrial presequence of cytochrome c oxidase subunit IV and model membranes.

The structural effect of the presequence of cytochrome oxidase subunit IV (p25) on multilamellar liposomes with different lipid compositions has been investigated using X-ray diffraction and electron microscopy. The presequence causes the disordering of the liposomes containing negatively charged lipids, without destabilizing the bilayer structure or destroying the multilamellar nature of the liposomes. In the systems containing only zwitterionic lipids, a small increase in the d-spacing (lamellar stacking spacing) is observed without any disorder effect suggesting a weaker interaction of the peptide and lipid. Circular Dichroism measurements of the peptide, in the presence and absence of the different lipid systems studied, show that the secondary structure of the peptide is modulated by the lipid environment. Considerable amounts of alpha-helix in the presequence is only observed in the systems containing negatively charged lipids. These are the same systems for which the disordering effect is observed with X-ray diffraction. It is proposed that p25 disorders the bilayer stacking by corrugating the membranes. The results are discussed in terms of the relevance of the specific lipid properties (e.g., electric charge and ability to form inverted phases) in determining how the peptide interacts with the lipid and affects its structural organization. It is suggested that the lipid properties relevant for the disordering effect induced by the peptide are the same as those involved in the formation of contact sites between mitochondrial membranes during the import of nuclear coded proteins.

Amino Acid Sequence↗
PubMed1998

Cystic tumours of the pancreas.

BACKGROUND: Cystic pancreatic tumours may be misdiagnosed as pseudocysts. METHODS: From August 1990 to January 1998, 21 patients (16 women) with a median age of 60 years underwent operation for a cystic mass in the pancreas with histological confirmation of neoplasia (six serous cystadenoma (SCA), three mucinous cystic adenoma (MCA), ten mucinous cystadenocarcinoma (MCAC), one ductal adenocarcinoma with cystic degeneration, one cystic islet cell tumour). RESULTS: While the lesion had been labelled as a pseudocyst in eight patients, only one patient (MCA in the pancreatic head) had had acute pancreatitis previously. In seven patients the computed tomogram (CT) lacked suspicious neoplastic features, while endoscopic retrograde cholangiopancreatography, angiography and percutaneous cyst fluid analysis were unhelpful or misleading in 16 of 18 investigations with respect to differentiating tumour from pseudocyst. Attempted operation for cure was performed in 18 patients despite diagnostic delays of up to 6 years and initial treatment with cystenterostomy in two cases. CONCLUSION: Retrospective review revealed that all 21 cystic neoplasms could be diagnosed before operation by a history excluding previous pancreatitis (20 of 21 patients) or a CT suspicious for neoplasia (14 of 21). The diagnosis relies more on absence of previous pancreatitis and a suspicious clinician who errs on the side of resecting a pseudocyst rather than watching or draining a cystic neoplasm.

Adenoma↗
PubMed1998

Prefabricated engineered bone flaps: an experimental model of tissue reconstruction in plastic surgery.

In light of the recently described experimental technique of in vivo bone reconstitution with biotechnologic methods (from bone marrow stromal cells) and the prefabrication flap procedures, the possibility to obtain autologous bone growth in a myocutaneous flap, thus creating a composite osteomyocutaneous preformed flap, is postulated. Human bone marrow stromal cells were delivered into the latissimus dorsi of athymic mice by a porous hydroxyapatite ceramic model. Eight weeks after the implantation, histologic examination revealed the presence of spongious bone tissue. A simple myocutaneous flap was thus transformed into a composite osteomyocutaneous flap. This flap is called the biotechnologic prefabricated flap, because it was the result of ex vivo expanded osteogenic precursor cells and in vivo bone tissue neoformation. The shape of the bone flap was exactly the same as the shape of the ceramic model used. A possible clinical application may be the correction of skeletal defects. The advantages of this procedure are simple surgical execution, the possibility of preshaping the graft to the exact characteristics of the defect, and the availability of autogenous donor tissue without donor site morbidity.

Animals↗
PubMed1998

Laparoscopy in the management of diaphragmatic rupture due to blunt trauma.

BACKGROUND: Traumatic diaphragmatic rupture remains a diagnostic challenge often unrecognized until laparotomy in over 40% of patients and the diagnosis is delayed in a further 15%. This report describes four patients diagnosed at laparoscopy with a ruptured diaphragm. METHODS: One patient had a left diaphragmatic rupture amenable to laparoscopic repair in the emergency setting. Three patients underwent laparoscopy 2, 7 and 10 days after injury which revealed two right-sided and one extensive left-sided rupture, respectively; each required open repair. RESULTS: While laparoscopy is an excellent diagnostic tool, particularly in the delayed setting, repair is not possible for right-sided ruptures because of the liver bulk. CONCLUSIONS: Thoracoscopy in the instance of delayed presentation may offer the best chance for minimal-access diagnosis and treatment when there is suspicion of a right-sided diaphragmatic rupture.

Adolescent↗
PubMed1998

Laparoscopic underrunning of bleeding duodenal ulceration: a minimalist approach to therapy.

Surgical management of bleeding duodenal ulcer has traditionally included a procedure to reduce gastric acid production to enable ulcer healing and reduce the likelihood of rebleeding. The availability of intravenous proton pump inhibitors in the peri-operative period may promote rapid ulcer healing and as a component of anti-Helicobacter eradication therapy greatly reduces the incidence of ulcer recurrence. Using this approach, six patients with actively bleeding duodenal ulcer underwent laparoscopic duodenotomy and attempted suturing of the bleeding site. One patient required conversion to open surgery and subsequently re-bled at 60 h, necessitating a partial (Billroth II) gastrectomy. In the remaining five patients suture control of bleeding and luminal closure were completed laparoscopically without complications. Laparoscopic repair of acutely bleeding duodenal ulcers is technically feasible and had a low complication rate in this small series.

Adult↗
PubMed1998

Phenotypic, morphologic changes and Ig secretion induced on B-NHL cells in vitro by interferon alpha and all-trans-retinoic acid: possible progression toward a more differentiated state.

Twenty-five B-cell-nonHodgkin's lymphomas (B-NHL): 6 lymphocytic, 2 centrocytic, 13 follicular, centrocytic/centroblastic, 2 lymphoplasmocytoid and 2 centroblastic were tested for their ability to acquire features of mature plasma cells under the effect of interferon alpha (final concentration, 600 UI/ml), all-trans-retinoic-acid (ATRA) (final concentration, 10(-6) mol/l) and the association of both. B-NHL cells were negatively purified (>99%) by an immunomagnetic method, cultured for 7 d with or without interferon and ATRA, then stained with anti-CD19, CD20, surface Ig, DR, CD38 and with anti-CD138 (syndecan-1) antibody-recognizing plasma cells. Ig production was estimated in culture supernatants by an ELISA method and changes in cell morphology were investigated on May-Grunwald-Giemsa-stained cytospin preparations. In all cases interferon and ATRA, alone or in association, were able to induce changes in the immunophenotypic profile, associated or not with morphologic changes and induction of Ig secretion. All changes were greatly variable from one to the other B-NHL sample and no relationship could be found between a particular pattern of change and the histological subtype. Interferon alpha was more potent than ATRA in inducing changes. In favour of a differentiation process, we observed a concomitant decrease of DR expression and increase of CD38 expression in 8 cases with interferon alpha, and in 4 cases with ATRA. Although interferon- or ATRA-treated cells did not display cytologic, functional features and changes of the immunophenotypic profile fully compatible with those of terminally differentiated cells, these results suggest a possible transition toward more differentiated elements, especially with interferon alpha.

Antigens, Surface↗