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M Dao

Publications and source records attributed to M Dao.

15 recordsLinked to original sources
PubMed2005

Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte.

We present a three-dimensional computational study of whole-cell equilibrium shape and deformation of human red blood cell (RBC) using spectrin-level energetics. Random network models consisting of degree-2, 3, ..., 9 junction complexes and spectrin links are used to populate spherical and biconcave surfaces and intermediate shapes, and coarse-grained molecular dynamics simulations are then performed with spectrin connectivities fixed. A sphere is first filled with cytosol and gradually deflated while preserving its total surface area, until cytosol volume consistent with the real RBC is reached. The equilibrium shape is determined through energy minimization by assuming that the spectrin tetramer links satisfy the worm-like chain free-energy model. Subsequently, direct stretching by optical tweezers of the initial equilibrium shape is simulated to extract the variation of axial and transverse diameters with the stretch force. At persistence length p = 7.5 nm for the spectrin tetramer molecule and corresponding in-plane shear modulus mu(0) approximately 8.3 microN/m, our models show reasonable agreement with recent experimental measurements on the large deformation of RBC with optical tweezers. We find that the choice of the reference state used for the in-plane elastic energy is critical for determining the equilibrium shape. If a position-independent material reference state such as a full sphere is used in defining the in-plane energy, then the bending modulus kappa needs to be at least a decade larger than the widely accepted value of 2 x 10(-19) J to stabilize the biconcave shape against the cup shape. We demonstrate through detailed computations that this paradox can be avoided by invoking the physical hypothesis that the spectrin network undergoes constant remodeling to always relax the in-plane shear elastic energy to zero at any macroscopic shape, at some slow characteristic timescale. We have devised and implemented a liquefied network structure evolution algorithm that relaxes shear stress everywhere in the network and generates cytoskeleton structures that mimic experimental observations.

Algorithms↗
PubMed2005

Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria.

We investigate connections between single-cell mechanical properties and subcellular structural reorganization from biochemical factors in the context of two distinctly different human diseases: gastrointestinal tumor and malaria. Although the cell lineages and the biochemical links to pathogenesis are vastly different in these two cases, we compare and contrast chemomechanical pathways whereby intracellular structural rearrangements lead to global changes in mechanical deformability of the cell. This single-cell biomechanical response, in turn, seems to mediate cell mobility and thereby facilitates disease progression in situations where the elastic modulus increases or decreases due to membrane or cytoskeleton reorganization. We first present new experiments on elastic response and energy dissipation under repeated tensile loading of epithelial pancreatic cancer cells in force- or displacement-control. Energy dissipation from repeated stretching significantly increases and the cell's elastic modulus decreases after treatment of Panc-1 pancreatic cancer cells with sphingosylphosphorylcholine (SPC), a bioactive lipid that influences cancer metastasis. When the cell is treated instead with lysophosphatidic acid, which facilitates actin stress fiber formation, neither energy dissipation nor modulus is noticeably affected. Integrating recent studies with our new observations, we ascribe these trends to possible SPC-induced reorganization primarily of keratin network to perinuclear region of cell; the intermediate filament fraction of the cytoskeleton thus appears to dominate deformability of the epithelial cell. Possible consequences of these results to cell mobility and cancer metastasis are postulated. We then turn attention to progressive changes in mechanical properties of the human red blood cell (RBC) infected with the malaria parasite Plasmodium falciparum. We present, for the first time, continuous force-displacement curves obtained from in-vitro deformation of RBC with optical tweezers for different intracellular developmental stages of parasite. The shear modulus of RBC is found to increase up to 10-fold during parasite development, which is a noticeably greater effect than that from prior estimates. By integrating our new experimental results with published literature on deformability of Plasmodium-harbouring RBC, we examine the biochemical conditions mediating increases or decreases in modulus, and their implications for disease progression. Some general perspectives on connections among structure, single-cell mechanical properties and biological responses associated with pathogenic processes are also provided in the context of the two diseases considered in this work.

Animals↗
PubMed2004

Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls.

Inflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparum malaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P = <0.001), IL-10 (1,099.3 versus 14.1; P = <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P = <0.001), and IL-12(p70) (48.9 versus 31.3; P = 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P = <0.001) and IL-10 (1,099.3 versus 133.9; P = <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P = <0.001) and IL-10 (1,405.6 versus 868.6; P = 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P = 0.03) and IL-10 (391.1 versus 1,160.9; P = 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P = 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparum malaria.

Adolescent↗
PubMed2004

Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers.

Studies of the deformation characteristics of single biological cells can offer insights into the connections among mechanical state, biochemical response and the onset and progression of diseases. Deformation imposed by optical tweezers provides a useful means for the study of single cell mechanics under a variety of well-controlled stress-states. In this paper, we first critically review recent advances in the study of single cell mechanics employing the optical tweezers method, and assess its significance and limitations in comparison to other experimental tools. We then present new experimental and computational results on shape evolution, force-extension curves, elastic properties and viscoelastic response of human red blood cells subjected to large elastic deformation using optical tweezers. Potential applications of the methods examined here to study diseased cells are also briefly addressed.

Elasticity↗
PubMed1999

Molecular control of cell cycle progression in primary human hematopoietic stem cells: methods to increase levels of retroviral-mediated transduction.

Pluripotent hematopoietic stem cells (HSC) are the ideal targets for gene transfer because they can repopulate a sublethally irradiated recipient, giving rise to all lineages of blood cells. Thus, introduction of a corrected gene into HSC (stem cell gene therapy) should ensure persistent transmission of the gene. To date, the most efficient mode of gene delivery is via Moloney murine leukemia virus (MoMuLV)-based retroviral vectors which stably integrate into the genome of the target cell. The quiescent nature of HSC and the fact that MoMuLV-based retroviral vectors can only integrate into dividing cells are major obstacles in gene therapy. While increasing efforts have been directed toward identifying growth factors which facilitate division of primary hematopoietic progenitor and stem cells, little is known about the molecular mechanisms which these cells use to enter cell cycle. In this review, we will discuss the correlation between the hematopoietic inhibitory and growth factors and their impact on the regulation of the cell cycle components.

Cell Cycle↗
PubMed1998

[Progressive noma: apropos of 27 cases seen at the National Hospital Center of Ouagadougou].

This retrospective study objects to report epidemiological profile, clinical display and take care of progressive noma at the National Hospital Center of Ouagadougou. We assign the term noma to the gangrenous gingivo-stomatitis occurring in a prone environment, leading in a few days into a sharp ulcer in the soft parts, accompanied by halitosis. This definition excludes noma like-lesions. 27 cases have been observed in the ENT department and the Paediatrics between 1991 and 1995. They were 17 boys and 10 girls aging between 2 and 8 years and most of them coming from families with modest income (76%). The consultation delay averaged 8 days. The research for associated pathologies showed 63% energizing and protein malnutrition. We only observed unilateral localisations and no case of extra-facial one. At the stage we received our patients, the gangrenous was formed and the aspect evoked noma right away. Quite a lot needs to be done for precocious diagnosis because it is at the beginning phase that best evolution is obtained. Even though no evidence of the responsibility of a specific pathogenic germ was established so far, nevertheless, the assumption that has more support remains that of a bacterial infection in a prone environment. The vital prognosis of the progressive noma appears to be much linked with intensive care and feeding again. The hope to see this poverty-linked pathology under control is essentially based on prevention: medical population information, medical personnel's awareness for early diagnosis and best take care of these patients, improvement of the living conditions of the people and the health care services.

Burkina Faso↗
PubMed1998

[Salivary gland tumors. Apropos of 48 surgical cases].

The interest of tumors of salivary gland has increased according to the nosology, diagnosis and therapeutic aspects. This study object to appreciate the frequency of this pathology at the ENT Department of the University Hospital Center of Ouagadougou and to report our experience in their diagnostic and therapeutic management. We have collected 48 cases, representing 2% of the department surgery activity and 7% of the tumors operated between 1985 and 1996. This report has concerned 32 parotid tumors (66.7%), 10 submaxillary tumors (20.8%), 6 minor gland tumors (12.5%). This series was composed of 28 women and 20 men with an average age of 41 years. Diagnosis management was based on clinical, radiologic and echographic examination. The correlation between preoperative and histological diagnosis was correct in 88.7% cases. Benign tumors represented 83.3% of the cases with essentially pleomorphic adenomas, and the malignant tumors 16.7% cases. Post operative evolution was simple in 85.4% cases. After 3 years, local recurrence occurred in 4 cases. The prognosis of malignant tumors has been unsatisfactory: the survival rate at 3 years has been 20%.

Adenoma↗
PubMed1998

[Short- and long-term results of parotidectomy, apropos of 24 cases at the Ougadougou University Hospital Center].

We reported the short and medium results of the 24 parodectomies performed at the ORL Department of the NHC of Ouagadougou between 1985 and 1993 in order to assess the frequency of the complications and to search for their causes. It is a retrospective study on 15 women and 9 men aging between 14 to 56 years. The research for the VII has been always done at the trunk. In the absence of an extemporan histological test, 3 exofacial parotidectomies have been performed for slight injuries of the superficial ear-lobe, 2 total parotidectomies in the other cases. All our sick persons have a 3-years recession. We registered: 1 case of post surgery haemorrhagia (4%) 2 cases of additional infection (8%) 3 cases of facial paralysis that are recessive or not (12.5%) 6 cases with Frei syndrome (25%). Multiple factors can explain the profile that follows surgery of our sick-persons. We insist on the fact that there is minimum specialist that are used to this kind of surgery and to the smallest of the technical board. Complications and after effects after-parotidectomy were in our view almost frequent in our conditions of work. It is true that it is a delicate surgery, but the after effects can be better improved by additional specialist in ORL and with an adequate equipment.

Adenocarcinoma↗
PubMed1994

[Cervical adenophlegmon (apropos of 57 cases)].

Neck adenitis remain a frequent occurrence in our areas. Within one year only, 57 cases were collected in the ORL department of University Hospital of Ouagadougou. Children were mostly affected (70% of cases) and the starting point or supposedly was mainly pharyngeal (67% of cases); streptococcus were the dominant microbes. Concerning the treatment, our preference was for wide antibiotherapy, in monotherapy but using wide spectrum, including staphylococcus aureus, due to its frequency in this pathology. But the primum movens remained the incision drainage. The post-operative period were regularly simple for our 57 patients.

Adolescent↗
PubMed1991

Designing assessment procedures for educationally at-risk Southeast Asian-American students.

This article discusses unique conditions of educational risk in the Southeast Asian-American student population. It points out the need to help traumatized refugee students deal with emotional difficulties before they can benefit from instruction. It includes a framework for assessing Southeast Asian-American students in which a shift in current assessment goals and practices is proposed. The article also addresses the issue of identifying skills previously developed in a different environment and explores an approach to help refugee children make the transition into the academic context.

Acculturation↗