Biomedical subjects

J M Mansour

Publications and source records attributed to J M Mansour.

At least 19 recordsLinked to original sources

PubMed2006

The physiology of fetal membrane rupture: insight gained from the determination of physical properties.

Premature rupture of the fetal membranes is a major cause of preterm birth and its associated infant morbidity and mortality. Recently, it has become clear that rupture of the fetal membranes, term or preterm, is not merely the result of the stretch and shear forces of uterine contractions, but is, in significant part, the consequence of a programmed weakening process. Work in the rat model has demonstrated that collagen remodeling, with activation of matrix metalloproteinases (MMPs), and apoptosis increase markedly in the amnion at end-gestation, suggesting that these processes are involved in fetal membrane weakening. We have developed fetal membrane strength testing equipment and a systematic tissue sampling methodology that has allowed us to demonstrate that term, non-labored, fetal membranes have a zone of weakness overlying the cervix, which contains biochemical markers of both collagen remodeling and apoptosis. These findings provide strong support for the concept of programmed fetal membrane weakening prior to labor. Our model has also been used to establish the physical properties of individual fetal membrane components (amnion, chorion), determine the sequence of events during the fetal membrane rupture process, and demonstrate that treatment of fetal membranes with TNF or IL-1beta, in vitro, induces weakness and the identical biochemical markers of collagen remodeling and apoptosis seen in the physiological weak zone. The ability to simultaneously correlate macroscopic physical properties with histological and biochemical fetal membrane characteristics, presents a unique perspective on the physiology of fetal membrane rupture.

Amnion↗

PubMed2004

Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor.

The etiology of fetal membrane (FM) rupture is unknown. A hypothesis that the FM weakens by a process of collagen remodeling and apoptosis to facilitate rupture has been proposed. Human FMs reportedly exhibit a zone of altered histology, postulated to be the FM rupture site, but concomitant FM weakness has not been demonstrated. We hypothesized that a discrete zone of FM with marked weakness, histological change, and evidence of remodeling and apoptosis, develops in late gestation in the FM overlying the cervix. FM tissue from women undergoing prelabor cesarean delivery were perioperatively marked to identify the FM overlying the cervix, cut with a procedure that facilitates remapping the rupture strength of FM pieces to their former location and orientation on a three-dimensional model, and tested for strength. A 10-cm FM zone centered at the cervical mark was compared with the remaining FM. Mean rupture strength within the cervical zone was 55% of the remaining FM. The cervical zone also exhibited increased MMP-9 protein, decreased tissue inhibitor of metalloproteinases-3 (TIMP-3) protein, and increased PARP cleavage coincident with the previously reported zone of altered histology. A discrete zone of weakness is present in term prelabor FMs overlying the cervix and has biochemical characteristics consistent with tissue remodeling and apoptosis.

Apoptosis↗

PubMed2000

Indentation of an osteochondral repair: sensitivity to experimental variables and boundary conditions.

The sensitivity of the affects of indenter radius, defect depth, cartilage permeability and flow boundary conditions, on the indentation testing of a repairing osteochondral defect was investigated. Since the boundary condition on the flow across the cartilage repair-subchondral bone interface is not known, the effects of two different conditions were investigated: free-flow and no-flow. A poroelastic finite element model of an osteochondral defect at different stages of the repair process was developed using dimensions typical of the rabbit knee. Results showed when the radius of the indenter was much less than the thickness of the cartilage the sensitivity of the indentation displacement to flow boundary conditions decreased. Simulated indentation displacement was insensitive to bone regeneration up to 50% of the initial defect depth, which suggests that only the properties of the material in the upper-half of the defect are being evaluated. Small variations in permeability had little affect on the simulated indentation. In a fully repaired defect, the simulated indentation is independent of the boundary condition. However, while the defect is in the process of repair and the regenerated cartilage is deeper than the host, indentation is sensitive to the flow boundary condition. Based on these results, and feasible experimental conditions, we conclude that the boundary condition on the repair-subchondral bone interface must be known in all cases except when the defect approaches full repair, if accurate estimates of material properties are to be obtained from indentation.

Animals↗

PubMed2000

Intrinsic and extrinsic contributions to the passive moment at the metacarpophalangeal joint.

The purpose of this investigation was to determine whether the passive range of motion at the finger joints is restricted more by intrinsic tissues (cross a single joint) or by extrinsic tissues (cross multiple joints). The passive moment at the metacarpophalangeal (MP) joint of the index finger was modeled as the sum of intrinsic and extrinsic components. The intrinsic component was modeled only as a function of MP joint angle. The extrinsic component was modeled as a function of MP joint angle and wrist angle. With the wrist fixed in seven different positions the passive moment at the MP joint of eight subjects was recorded as the finger was rotated through its range at a constant rate. The moment-angle data were fit by the model and the extrinsic and intrinsic components were calculated for a range of MP joint angles and wrist positions. With the MP joint near its extension limit, the median percent extrinsic contribution was 94% with the wrist extended 60 degrees and 14% with the wrist flexed 60 degrees. These percentages were 40 and 88%, respectively, with the MP joint near its flexion limit. Our findings indicate that at most wrist angles the extrinsic tissues offer greater restraint at the limits of MP joint extension and flexion than the intrinsic tissues. The intrinsic tissues predominate when the wrist is flexed or extended enough to slacken the extrinsic tissues. Additional characteristics of intrinsic and extrinsic tissues can be deduced by examining the parameter values calculated by the model.

Adult↗

PubMed2000

Schistosoma mansoni phosphofructokinase: immunolocalization in the tegument and immunogenicity.

Schistosoma mansoni depends for its survival on glycolysis. Two glycolytic enzymes, glyceraldehyde-3P-dehydrogenase and triose-phosphate dehydrogenase, found in both the adult and schistosomular tegument, have been reported to confer partial protection against cercarial infection. This paper describes the immunogenic properties of phosphofructokinase (PFK), a rate-limiting enzyme of glycolysis, and its localization in the tegument and adjacent tissues. Recombinant schistosome PFK was used as antigen. A polyclonal antibody against purified PFK from Fasciola hepatica was affinity purified using recombinant PFK and used in combination with immunogold labelling to identify PFK by transmission electron microscopy in cryosections. In both adult worms and in schistosomula most immunogold label localized in the cytoplasmic syncytial region with less being found in the tegument. There was no significant PFK localization within or external to the outer membrane. Sera from mice immunized with recombinant S. mansoni PFK with Freund's adjuvant or alum plus rIL-12 demonstrated high titres of anti-PFK IgG, but no protection against cercarial infection. Sera from mice that were acutely or chronically infected or multiply exposed to irradiated cercariae did not recognize recombinant schistosome PFK in either Western blotting or ELISA. Similarly, sera from humans infected with S. mansoni did not recognize PFK. We conclude that in spite of the high immunogenicity of rPFK in mice, it is not a significant immunogen during the course of infection and does not confer protection from schistosomiasis. One main difference between PFK and the other 2 glycolytic enzymes seems to be the inaccessibility of PFK to the outside surface of the tegument.

Animals↗

PubMed1998

Reduction in tensile strength of cartilage precedes surface damage under repeated compressive loading in vitro.

An experimental protocol for the fatiguing and tensile testing of articular cartilage has been established. Samples were taken from the interpatellar groove of bovine femurs collected post-slaughter, split into two test groups and subjected to a cyclically varying compressive load of approximately 65 N for 64,800 cycles or 97,200 cycles. The cartilage was then removed from the underlying bone and two specimens, one from the indented region and one from an unindented region - the control, were taken from it and prepared for subsequent tensile testing using notched specimens. From data collected during tensile testing, a value of maximum tensile stress was calculated for each sample. The underlying bone was examined for evidence of microdamage using the basic fuchsin method. A decrease in values of maximum tensile stress (p < 0.05) for the indented sample of each paired group of samples loaded for 97,200 cycles was found. In contrast, those fatigued for only 64,800 cycles showed no such difference. Examination of the underlying bone of these specimens revealed no evidence of trabecular failure and crack formation beneath both the indented and control regions. It is postulated that the fatiguing process used in this experiment induces trauma in the cartilage causing a weakening of the interfibril connections which link collagen fibrils in the matrix, leading to a reduction in tensile strength. This weakening occurs, however, without the appearance of fibrillation on the cartilage surface or any evidence of failure in the bony structure which supports it.

Animals↗

PubMed1998

Repair of large full-thickness articular cartilage defects with allograft articular chondrocytes embedded in a collagen gel.

Full-thickness articular cartilage defects are a major clinical problem; however, presently there is no treatment available to regeneratively repair these lesions. The current therapeutic approach is to drill the base of the defect to expose the subchondral bone with its cells and growth factors. This usually results in a repair tissue of fibrocartilage that functions poorly in the loaded joint environment. The use of phenotypically appropriate chondrocytes embedded in a collagen gel delivery vehicle may provide a method that could be used to repair full-thickness articular cartilage defects with functionally satisfactory hyaline cartilage. Allograft articular chondrocytes embedded in a type I collagen gel were transplanted into large (6 x 3 x 3 mm), full-thickness articular cartilage defects in condylar and patellar weight-bearing surfaces to develop clinically applicable methods to repair articular cartilage defects. Chondrocytes were isolated from the articular cartilage of 4-week-old New Zealand rabbits and embedded in type I collagen gels. This composite was transplanted into a full-thickness defect on the medial femoral condyle and patellar groove of adolescent host rabbits. The repair cartilage was assessed histologically by a semiquantitative scoring system and biomechanically with a microindentation technique of specimens 4-48 weeks after chondrocyte transplantation. Defects in both locations were repaired with histologically apparent hyaline cartilage observed from as early as 4 weeks until 48 weeks after transplantation. The repair cartilage in the medial femoral condyle was more irregular than in the patellar groove, but in all other respects was similar. The grafted tissue did not remodel and differentiate into the morphological zones seen in normal articular cartilage. No tidemark or subchondral bony plate formed even 48 weeks after transplantation. Biomechanically, the repaired cartilage demonstrated indentation values similar to normal articular cartilage 12 weeks after transplantation and remained the same 48 weeks after transplantation. By contrast, the control (i.e., empty) defects healed with tissue that exhibited very poor metachromatic staining and exhibited very high indentation values. Incomplete bonding of the repair tissue to the normal cartilage was seen, and the surface was significantly irregular with major discontinuities. These observations provide the basis for considering the use of allograft articular chondrocytes to repair articular cartilage defects in the weight-bearing regions of the knee.

Animals↗

PubMed1996

Purification, kinetics and inhibition by antimonials of recombinant phosphofructokinase from Schistosoma mansoni.

We reported before on the cloning of a cDNA encoding S. mansoni PFK. In the present investigation we established optimal conditions for expression of the enzyme in insect cells with high yield. The recombinant PFK was purified to homogeneity. Kinetic properties of the pure enzyme were studied with respect to its two substrates, Fru-6-P and ATP, and were compared with properties of mammalian PFK. ATP inhibited the parasite enzyme only at concentrations higher than those which inhibited mammalian muscle PFK. Saturation curves for Fru-6-P showed typical cooperative kinetics. AMP, cAMP and Fru-2,6-bisP activated the enzyme causing reduced apparent Km for Fru-6-P and an increase in maximal activity. Both ATP inhibition and cooperative kinetics for Fru-6-P occur at both pH 6.9 and 8.2. This is a distinct difference from the mammalian enzyme which shows these kinetic properties only at neutral or slightly acidic pH, but not at an alkaline pH. Recombinant PFK is more sensitive to inhibition by the trivalent antimonials, antimony potassium tartrate and Stibophen, than is the mammalian heart muscle enzyme. The inhibition is at least partially antagonized by the sulfhydryl protective reagent, dithiothreitol.

Animals↗

PubMed1996

An experimentally based nonlinear viscoelastic model of joint passive moment.

Previous investigations have not converged on a generally accepted model of the dissipative part of joint passive moment. To provide a basis for developing a model, a series of measurements were performed to characterize the passive moment at the metacarpophalangeal joint of the index finger. Two measurement procedures were used, one in moment relaxation over a range of fixed joint angles and the other at a series of constant joint velocities. Fung's quasi-linear viscoelastic theory motivated the development of the passive moment model. Using this approach, it was not necessary to make restrictive assumptions regarding the viscoelastic behavior of the passive moment. The generality of the formulation allowed specific functions to be chosen based on experimental data rather than finding coefficients which attempted to fit a preselected model of the data. It was shown that a nonlinear viscoelastic model described the passive stiffness. No significant frictional effects were found. Of particular importance was the nonlinear behavior of the dissipative part of the passive moment which was modeled by joint speed raised to a power less than one. This result could explain the differing findings among previous investigations, and may have important implications for control of limb movement.

Adult↗

PubMed1995

Some phosphonic acid analogs as inhibitors of pyrophosphate-dependent phosphofructokinase, a novel target in Toxoplasma gondii.

Pyrophosphate-dependent phosphofructokinase (PPi-PFK) was identified previously in Toxoplasma gondii as the only kinase that phosphorylates fructose-6-P to fructose-1,6-bisP. Since such an enzyme is not present in mammals, it was considered to be a good target for prospective selective inhibitors of the parasite. We have examined the effects of several phosphonic acid derivatives, analogs of pyrophosphate, on PPi-PFK activity, as well as on the replication of T. gondii in human foreskin fibroblast (HFF) cells. The most active compound in inhibiting PPi-PFK was tetrasodium carbonyldiphosphonate. Several bisphosphonates and related arylhydrazones showed inhibition of the enzyme, but with higher IC50 values. Although several phosphonoacetic acid derivatives also inhibited PPi-PFK, as a group they were less potent than the bisphosphonate derivatives. Comparison among the structures of various inhibitors and their effects against PPi-PFK indicates that a carbonyl (C=O) or amino (C=N) group between two phosphoryl moieties is associated with more potent enzyme inhibiton. Tetrasodium carbonyldiphosphonate did not show a significant effect against replication of T. gondii cells, probably because, as a charged molecule, it could not cross the cell membrane to reach the intracellular parasite. Tetraisopropyl carbonyldiphosphonate 2,4-dinitrophenylhydrazone showed some selective inhibitory effect against replication of the parasite in the HFF cells and protected the mammalian cells from damage by T. gondii. The results indicate that carbonyldiphosphonic acid is a good prototype compound that is amenable to chemical manipulation, which, in turn, may optimize selective inhibition of T. gondii PPi-PFK and increase accessibility to the intracellular parasite.

Adenosine Triphosphate↗

PubMed1994

Biomechanical, radiologic, and histopathologic correlations in the pathogenesis of experimental intervertebral disc disease.

STUDY DESIGN: The desert sand rat, an animal model for spinal degenerative disc disease, was studied for biomechanical, histologic, and radiographic characteristics. Load deformation curves with peak force and force decay, hematoxylin-eosin-stained sections, and lateral radiographs were correlated. OBJECTIVES: The hypothesis that the subchondral bone response preceded or contributed to the degenerative disc disease seen in the desert sand rat was tested. SUMMARY OF BACKGROUND DATA: Intervertebral disc disease spontaneously develops in the desert sand rat during its lifetime. Approximately 50% will have significant disc disease by age 18 months. Previous studies have found metabolic and histologic changes associated with intervertebral disc degeneration in the sand rat. METHODS: Desert sand rats were killed at 3-, 9-, 15-, and 18-month intervals and tested in Rheometrics Solid Analyzer with nondestructive step strain loading to obtain a load deformation curve. Radiographs and histologic sections of each animal were compared. Peak force and force decay were analyzed by level and by age. Analysis of variance and Tukey's methods were applied to data. RESULTS: There were no statistically significant differences in biomechanical data. No histologic changes were noted in the study groups up to 18 months of age. Radiographic differences characterized by subchondral bony sclerosis were noted by 18 months of age. No trends were noted when radiographic grades were compared with force data. CONCLUSIONS: The absence of biomechanical histologic changes in the intervertebral disc per se from 3 through 18 months, with radiographic changes in the subchondral bone, supports the hypothesis that the earliest changes in intervertebral disc disease in this animal model are related to the subchondral bone response.

Animals↗

PubMed1994

Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage.

UNLABELLED: Osteochondral progenitor cells were used to repair large, full-thickness defects of the articular cartilage that had been created in the knees of rabbits. Adherent cells from bone marrow, or cells from the periosteum that had been liberated from connective tissue by collagenase digestion, were grown in culture, dispersed in a type-I collagen gel, and transplanted into a large (three-by-six-millimeter), full-thickness (three-millimeter) defect in the weight-bearing surface of the medial femoral condyle. The contralateral knee served as a control: either the defect in that knee was left empty or a cell-free collagen gel was implanted. The periosteal and the bone-marrow-derived cells showed similar patterns of differentiation into articular cartilage and subchondral bone. Specimens of reparative tissue were analyzed with use of a semiquantitative histological grading system and by mechanical testing with employment of a porous indenter to measure the compliance of the tissue at intervals until twenty-four weeks after the operation. There was no apparent difference between the results obtained with the cells from the bone marrow and those from the periosteum. As early as two weeks after transplantation, the autologous osteochondral progenitor cells had uniformly differentiated into chondrocytes throughout the defects. This repair cartilage was subsequently replaced with bone in a proximal-to-distal direction, until, at twenty-four weeks after transplantation, the subchondral bone was completely repaired, without loss of overlying articular cartilage. The mechanical testing data were a useful index of the quality of the long-term repair. Twenty-four weeks after transplantation, the reparative tissue of both the bone-marrow and the periosteal cells was stiffer and less compliant than the tissue derived from the empty defects but less stiff and more compliant than normal cartilage. CLINICAL RELEVANCE: The current modalities for the repair of defects of the articular cartilage have many disadvantages. The transplantation of progenitor cells that will form cartilage and bone offers a possible alternative to these methods. As demonstrated in this report, autologous, bone-marrow-derived, osteochondral progenitor cells can be isolated and grown in vitro without the loss of their capacity to differentiate into cartilage or bone. Sufficient autologous cells can be generated to initiate the repair of articular cartilage and the reformation of subchondral bone. The repair tissues appear to undergo the same developmental transitions that originally led to the formation of articular tissue in the embryo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

A method for obtaining repeatable measurements of the tensile properties of skin at low strain.

Initial attempts at measuring the low strain tensile properties of skin led to results which were not repeatable. It appeared that strains induced in the sample due to the handling needed to mount it in a simple clamp led to the low precision of the test. A new method which minimized the manipulation needed to mount a sample in a testing machine was then developed. Using this method the skin was aligned with a set of grips in a saline bath. When aligned, the saline was removed and the sample clamped in the grips without the need for additional handling. This approach produced a marked improvement in the repeatability of the tensile properties of skin at low strains.

Animals↗

PubMed1991

Dynamic measurement of the viscoelastic properties of skin.

A wave propagation technique was used to measure the dynamic viscoelastic properties of excised skin when subjected to a low incremental strain. The propagation velocity, attenuation, and storage and loss moduli were determined from measured characteristics of a pulse propagating along a strip of skin. Experiments were conducted with the skin subjected to static stresses of 1500 Pa and 20,000 Pa. At low static stresses the skin response was viscoelastic with a loss tangent of approximately 0.6. In the frequency range of 0-1000 Hz, the wave velocity was relatively constant while the attenuation increased roughly linearly with frequency. However, results depended on the static stress. At the higher stress level the velocity was greater and the attenuation less than at the lower stress. At low stresses both the storage and loss moduli were relatively constant over the frequency range tested. The strong viscoelastic behavior of the tissue at higher frequencies is not predicted from models of the tissue determined from quasi-static test methods. In selecting a model to describe the behavior of skin, the test methods used for establishing the model must be consistent with its intended application.

Animals↗

PubMed1991

The effects of layer properties on shear disturbance propagation in skin.

The effects of the stratum corneum and dermis on shear wave propagation along the skin surface was investigated using a mathematical model. The skin was modeled as two distinct viscoelastic layers, one representing the stratum corneum and the other representing the dermis. The layers were supported by a semi-infinite visco-elastic half-space representing the subcutaneous fat. Physical and mechanical properties of the materials in the model were determined from the literature and from our own experimental measurements. Although the stratum corneum is very thin (12-15 microns), results showed that it could have a strong effect on the wave propagation due to its high stiffness relative to the dermis. Results of the analysis are discussed with respect to an experimental procedure used to determine age-related changes in mechanical properties of skin.

Aging↗

PubMed1990

Analysis of shear wave propagation in skin; application to an experimental procedure.

An analysis of an experimental procedure used to determine age-related changes in the skin was performed. The experiment is based on the propagation of a shear wave through the skin. The analysis of the experiment was used to determine the effects of parameters such as properties of the skin and subcutaneous fat, skin thickness and experimental conditions on the propagation. Computer simulations showed that at lower frequencies (less than 1000 Hz), measured results depended strongly on skin thickness, while at higher frequencies (2000 Hz) the results were relatively insensitive to both skin thickness and the properties of the subcutaneous fat. Results also depended upon the distance between the applied shear disturbance and the measurement point. The analysis suggests that higher frequency (2000 Hz) experimental results are more indicative of mechanical properties of skin than lower frequency (less than 1000 Hz) results.

Aging↗

PubMed1989

Identification of GTP-binding proteins in Fasciola hepatica and Schistosoma mansoni by immunoblotting.

Both the liver fluke Fasciola hepatica and the blood fluke Schistosoma mansoni have GTP-binding proteins which are part of the trans-membrane signalling system. These proteins require GTP in order to interact with the catalytic subunit of adenylate cyclase. The technique of immunoblotting was used in order to distinguish the GTP-binding proteins Gs, Gi, and Go. Immunoblotting was carried out using antisera prepared against peptides deduced from bovine cDNA clones specific for alpha or beta subunits of known G proteins. A 41-kDa Gs alpha has been identified in S. mansoni and a 42.5-kDa Gs alpha in F. hepatica. A 41-kDa Go alpha was found in both parasites. A 36-kDa G beta was identified in both parasites using antiserum made against bovine transducin.

Amino Acid Sequence↗

PubMed1989

Age-dependent changes in the shear wave propagation through human skin.

We studied the potential use of the in vivo frequency response of human volar forearm skin as a means for evaluating skin age. The velocity and damping length of waves on the skin surface were correlated with chronological age. One hundred and fifty subjects from 1 to 95 years of age were studied. For the frequency spectrum from 800 to 2000 Hz, there was a linear correlation between the velocity of propagation and age. At 2000 Hz, the y intercept was 11.4 m/second and the slope was 0.245 m/second/year, r = 0.5500, p less than 1 x 10(-7). There was no correlation of velocity with sex, skin color, obesity, sun exposure, physical activity, or inpatient status.

Adolescent↗