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Raymond Coleman

Publications and source records attributed to Raymond Coleman.

At least 19 recordsLinked to original sources
PubMed2006

Atherosclerosis and the protective role played by different proteins in apolipoprotein E-deficient mice.

The aim of the present study was to analyze the early events in atherogenesis and the role of pro- or anti-atherosclerotic proteins in the development of atherosclerotic lesions. We used apolipoprotein E-deficient (E(0)) mice that spontaneously develop hypercholesterolemia and atherosclerotic lesions in the aorta in a time-dependent manner. Aortas of mice aged 6, 8, 10 and 12 weeks were examined to determine histopathological changes. In mice aged 8-12 weeks, developing atherosclerotic lesions were present in different regions of the aortas. These lesions protruded into the lumen of the vessel and showed lipid deposits, lipid-filled macrophages and extensive accumulation of collagen and elastic fibers throughout the entire arterial wall. A parallel immunohistochemical study included analysis of three proteins known to be involved in atherosclerosis, i.e. inducible nitric oxide synthase (iNOS, NOS2), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP2). Increased immunolabelling of iNOS and VEGF accompanied atherosclerosis development in E(0) mice aged 8, 10 and 12 weeks. On the contrary, immunolabelling for MMP2 was negative in E(0) mice aged 10 and 12 weeks. Our results indicate morphological alterations in the Tunica intima and Tunica media of atherosclerotic aortas and possible protective roles for iNOS and VEGF proteins against atherosclerosis development. These data may be relevant for developing therapeutic strategies for atherosclerosis development.

Animals↗
PubMed2006

A mouse model for human atherosclerosis: long-term histopathological study of lesion development in the aortic arch of apolipoprotein E-deficient (E0) mice.

Apolipoprotein E-deficient mice, since their introduction in the early 1990s, have proved to be a very popular model for studying spontaneous hypercholesterolemia and the subsequent development of atherosclerotic lesions. The pathogenesis of atherosclerotic lesions in these mice mimics that found in humans on a very short time-scale. Atherosclerotic lesion development is especially prominent in the aortic arch. We have followed the progressive histopathological development of atherosclerotic lesions in the aortic arch of apolipoprotein E-deficient mice aged from 6 weeks to 18 months in 1 microm epoxy-resin sections stained with alkaline toluidine blue, which gives greatly improved resolution over wax sections. During the early stages of lesion formation, lipid-filled macrophages appear in the subendothelium, and accumulate leading to "fatty streaks". Macrophage degeneration and the formation of lipid pools are accompanied by accumulation of cholesterol deposits. Disruptions of elastic laminae of the Tunica media are accompanied by structural changes in the myocytes. More advanced lesions involve fibrous cap development, calcification of the vessel wall and progressive occlusion of the lumen. Unstable plaque may also be found. Various approaches for quantitative determination of lesion size are considered. The study provides a histopathological baseline for spontaneous atherosclerosis associated with hypercholesterolemia, which can be used in connection with experimental interventional studies on the efficacy of drugs or foodstuffs in retardation of atherosclerosis.

Animals↗
PubMed2006

A comparative study of organized class-based exercise programs versus individual home-based exercise programs for elderly patients following hip surgery.

PURPOSE: To evaluate and compare the effectiveness of supervised and non-supervised exercise programs for improving health and rehabilitation outcomes for elderly persons following hip surgery. METHOD: Prospective, descriptive and quantitative study involving two groups: The class-based program (group A, n = 34: 21 females, 13 males, mean age 79.2 years +/- 5.23) was directed and administered in the outpatient clinic, and a home-based program (group B, n = 29, 17 females, 12 males, mean age 80.3 years +/- 5.74) which administered in the patient's home. Sixty three elderly patients began at a period of 2 weeks post hip surgery for open reduction with internal fixation. The training period took place for 14 consecutive weeks. The main outcome measures include results from physical performance test, functional reach test and short form-36 health survey questionnaire. RESULTS: Fifty five patients completed the exercise program. No significant difference according to gender or Body Mass Index was found between the groups. At the conclusion of 14 weeks of exercise training both groups demonstrated improvement in physical function. However, only 4 of 6 total tasks of a physical performance test were improved in the home-based group compared to improvement in all 6 tasks for the class-based group. The SF-36 scores and the functional reach test indicated that the class-based subjects also presented significant gains in contrast to no significant changes in the home exercise group. CONCLUSIONS: Both groups demonstrated improvement in a number of issues. However, there appears to be more positive health outcomes presented by the participants in the supervised/class-based group when compared to the non-supervised/home-based group. And therefore, patients may select to participate to either a home-based or class-based regime. The clinical relevance is the significant of the necessity for close supervision by a professional therapist. In addition, the results could have some political and economical implications on the healthcare system.

Aged↗
PubMed2006

The influence of a human embryonic stem cell-derived microenvironment on targeting of human solid tumor xenografts.

The awareness of the important role that the surrounding tissue microenvironment and stromal response play in the process of tumorigenesis has grown as a result of in vivo models of tumor xenograft growth in immunocompromised mice. In the current study, we used human embryonic stem cells in order to study the interactions of tumor cells with the surrounding microenvironment of differentiated human cell tissues and structures. Several cancer cell types stably expressing an H2A-green fluorescence protein fusion protein, which allowed tracking of tumor cells, were injected into mature teratomas and developed into tumors. The salient findings were: (a) the observation of growth of tumor cells with high proliferative capacity within the differentiated microenvironment of the teratoma, (b) the identification of invasion by tumor cells into surrounding differentiated teratoma structures, and (c) the identification of blood vessels of human teratoma origin, growing adjacent to and within the cancer cell-derived tumor. Mouse embryonic stem cell-derived teratomas also supported cancer cell growth, but provided a less suitable model for human tumorigenesis studies. Anticancer immunotherapy treatment directed against A431 epidermoid carcinoma cell-related epitopes induced the complete regression of A431-derived tumor xenografts following direct i.m. injection in immunocompromised mice, as opposed to corresponding tumors growing within a human embryonic stem cell-derived microenvironment, wherein remnant foci of viable tumor cells were detected and resulted in tumor recurrence. We propose using this novel experimental model as a preclinical platform for investigating and manipulating the stromal response in tumor cell growth as an additional tool in cancer research.

Animals↗
PubMed2006

Pomegranate byproduct administration to apolipoprotein e-deficient mice attenuates atherosclerosis development as a result of decreased macrophage oxidative stress and reduced cellular uptake of oxidized low-density lipoprotein.

The effects of a pomegranate byproduct (PBP, which includes the whole pomegranate fruit left after juice preparation) on atherosclerosis development in apolipoprotein E-deficient (E degrees ) mice were studied. Consumption of PBP (17 or 51.5 microg of gallic acid equiv/kg/day) by the mice resulted in a significant reduction in atherosclerotic lesion size by up to 57%. PBP consumption significantly reduced oxidative stress in the mice peritoneal macrophages (MPM): Cellular lipid peroxide content decreased by up to 42%, the reduced glutathione levels increased by up to 53%, and paraoxonase 2 lactonase activity increased by up to 50%, as compared to MPM from E degrees mice that consumed only water. Furthermore, oxidized low-density lipoprotein (Ox-LDL) uptake by the MPM was reduced by up to 19%. Similar results were observed also in vitro. Treatment of J774A.1 macrophages with PBP (10 or 50 micromol/L of total polyphenols) significantly decreased both cellular total peroxide content and Ox-LDL uptake. It was thus concluded that PBP significantly attenuates atherosclerosis development by its antioxidant properties.

Animals↗
PubMed2006

Chronic acidosis-induced growth retardation is mediated by proton-induced expression of Gs protein.

UNLABELLED: The etiology of skeletal growth retardation accompanying metabolic acidosis is not clear. Using ex vivo models for endochondral ossification, we showed that the cAMP/PKA pathway, probably triggered by proton sensitive G-protein-coupled receptors, is responsible for impaired skeletal growth in acidosis. INTRODUCTION: Chronic metabolic acidosis (CMA) is very often accompanied by skeletal growth retardation. We have previously shown in an ex vivo model of endochondral ossification that murine mandibular condyles subjected to acidic conditions exhibit growth retardation accompanied by a decline of insulin-like growth factor-I (IGF-I) and its receptors. PTH-induced ameliorative effects on the CMA-induced growth retardation of the mandibular condyle are partially mediated by protein kinase C (PKC). In this study we explored the mechanisms underlying the acidosis-induced growth retardation; in particular, the involvement of the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) cellular pathway in the process. MATERIALS AND METHODS: Mandibular condyles from neonatal mice or mandibular condyle derived chondrocytes (MCDCs) were incubated for 3 days under either control or acidic conditions or in the presence of cAMP-regulating factors (cAMPrf) such as forskolin, iso-butyl methyl xanthine (IBMX), or 8-Br cAMP. The effects on proliferation and differentiation of the cultures as well as on phosphorylation of cAMP responsive element binding protein (CREB) and increased expression of the alpha subunit, Gs were determined. The intracellular pH was detected using the acridine orange assay. RESULTS: Our results show that, under acidic conditions, PKA levels were increased. H89 abolished the adverse effects of acidosis on condylar development and restored IGF-I and IGF-I receptors (IGF-IR) levels. The inhibitory effects of acidosis on proliferation and differentiation of cartilaginous cells were mimicked by cAMPrf. We have also shown that acidosis stimulates activation of Gs trimeric protein and CREB phosphorylation. GDPbetaS--a Gs antagonist--abolished the acidosis-induced condylar growth arrest. Using an acridine orange assay, we showed that the intracellular environment is not acidified under acidic conditions. CONCLUSIONS: Our results indicate that the adverse effects of acidosis on skeletal growth centers are mediated at least in part by the cAMP/PKA cellular pathway. We speculate that high proton concentrations exerted by acidosis conditions stimulate proton sensitive G-protein-coupled receptors, which are mediated by the cellular cAMP/PKA pathway and induce skeletal growth retardation.

Acidosis↗
PubMed2005

The 1,4,5-inositol trisphosphate pathway is a key component in Fas-mediated hypertrophy in neonatal rat ventricular myocytes.

OBJECTIVE: Cardiac hypertrophy is a compensatory response to increased mechanical load. Since Fas receptor activation is an important component in hypertrophy induced by pressure- and volume-overload, deciphering the underlying signaling pathways is of prime importance. Based on our previous work showing that in mice and rats ventricular myocytes the electrophysiological disturbances and diastolic [Ca2+]i-rise caused by 3 h of Fas activation are dependent on the Fas-->phospholipase C (PLC)-->1,4,5-inositol trisphosphate (1,4,5-IP3)-->sarcoplasmic reticulum (SR) [Ca2+]i release pathway, we tested the hypothesis that this pathway is also critical for Fas-mediated hypertrophy. METHODS: The effects of 24 h Fas activation in cultured neonatal rat ventricular myocytes (NRVM) were analyzed by means of RT-PCR, Western blot, immunofluorescence and fura-2 fluorescence. RESULTS: Fas activation increased nuclei surface area, atrial natriuretic peptide and connexin43 (Cx43) mRNA, the protein levels of total Cx43 and non-phosphorylated Cx43, and sarcomeric actin, all indicating hypertrophy. Concomitantly, Fas activation decreased mRNA of SERCA2a, the ryanodine receptor (RyR) and nuclear IP3R3. Further, Fas activation caused NFAT nuclear translocation. The hypertrophy was abolished by U73122, xestospongin C (blockers of the 1,4,5-IP3 pathway), genistein and by the PI3K blocker LY294002. CONCLUSIONS: Fas-mediated hypertrophy is dependent on the 1,4,5-IP3 pathway, which is functionally inter-connected to the PI3K/AKT/GSK3beta pathway. Both pathways act in concert to cause NFAT nuclear translocation and subsequent hypertrophy.

Animals↗
PubMed2005

Macrophage foam-cell formation in streptozotocin-induced diabetic mice: stimulatory effect of glucose.

BACKGROUND: Diabetes is associated with an increased risk for atherosclerosis. We investigated the effect of diabetes induction on atherogenesis and on macrophage-foam cell formation. METHODS AND RESULTS: Atherosclerotic apolipoprotein-E-deficient mice were converted into diabetic mice by streptozotocin injection. Aortic atherosclerotic lesion area was significantly enhanced by 67% and 106% in mice that were diabetic for 1 and 3 months, respectively, compared to the non-diabetic mice. Moreover, mouse peritoneal macrophages (MPM) from diabetic mice for 1 and 3 months exhibit higher lipid peroxides content by 55% and 63%, respectively, in association with the MPM glucose content. Oxidized LDL (Ox-LDL) uptake by MPM obtained from diabetic mice for 1 and 3 months was significantly increased by 36% and 45%, respectively, in association with the increased macrophage cholesterol content. To determine whether the accelerated foam cell formation in diabetic mice could result from a direct effect of glucose on macrophages, J-774-A.1 macrophages were incubated with increasing glucose concentrations (2.5-62 mM). Glucose-enriched macrophages exhibit dose-dependent higher peroxides content up to 7.5-fold and increased Ox-LDL cellular uptake associated with up-regulation of the scavenger receptor CD36 at the mRNA level. CONCLUSION: Induction of diabetes in atherosclerotic mice led to an accelerated atherosclerosis and macrophage-derived foam cell formation, probably by involving a glucose-dependent related mechanism.

Animals↗
PubMed2005

The effect of hindlimb immobilization on acid phosphatase, metalloproteinases and nuclear factor-kappaB in muscles of young and old rats.

Age-associated muscle wasting (sarcopenia of old age) is a major problem in elderly people, however, the mechanisms of muscle proteolysis in aging remain obscure and enigmatic. Possible reasons for loss of skeletal muscle mass with aging may be attributed to multiple and complex proteolytic systems. The purpose of the present study was to explore the kinetics of activation of extracellular hydrolytic and proteolytic systems in muscles of hindlimbs immobilized by external fixation of 24-month-old female Wistar rats, in comparison with those of 6-month-old rats. Results show that elevated acid phosphatase activities (lysosomal hydrolytic enzyme activated mainly in macrophages) in immobilized limb muscles of young animals, differ from old animals. In young rats external fixation resulted in significantly elevated acid phosphatase activities (50-55%; p<0.05) after 4 weeks of immobilization, whereas in old animals similar increases were observed already during the first and second weeks of immobilization. The extracellular proteolytic enzymes, matrix metalloproteinases (MMP-2 and -9), were also differentially activated in old animals compared to young animals. In young animals, as shown in previous studies, both MMP-2 and -9 activities were elevated significantly in immobilized muscles. In this study of old animals, only MMP-2 activity was detected, with no significant elevation in the immobilized muscles of old animals. In addition, the levels of the transcription factor Nuclear Factor-kappaB (NF-kappaB) in nuclear extracts of old rat muscles, as detected by ELISA, showed a biphasic pattern after immobilization, suggesting that NF-kappaB could be activated by different processes in the atrophy process, at least in the old age. In conclusion, it seems that the kinetics of activation of extracellular hydrolytic and proteolytic systems differ in muscles of old animals compared to young animals.

Acid Phosphatase↗
PubMed2005

Grape powder polyphenols attenuate atherosclerosis development in apolipoprotein E deficient (E0) mice and reduce macrophage atherogenicity.

The beneficial health effects of red wine have been attributed to the antioxidant activity of its polyphenols. The present study investigated the effects of a standardized freeze-dried powder made from fresh grapes, rich in grape-specific polyphenols and free of alcohol, on oxidative stress, atherogenicity of macrophages, and the development of atherosclerotic lesions in apolipoprotein E deficient (E(0)) mice. Thirty E(0) mice were assigned to 3 groups. Mice consumed water alone (control), 150 mug total polyphenols/d in the form of grape powder (grape powder), or the equivalent amount of glucose and fructose (placebo) in drinking water for 10 wk. Consumption of grape powder reduced the atherosclerotic lesion area by 41% (P < 0.0002) compared to the control or placebo mice. The antiatherosclerotic effect was at least partly due to a significant 8% reduction in serum oxidative stress, an up to 22% increase in serum antioxidant capacity, a significant 33% reduction in macrophage uptake of oxidized LDL, and a 25% decrease in macrophage-mediated oxidation of LDL relative to controls. Grape powder directly protected both plasma LDL and macrophages from oxidative stress in vitro. We conclude that polyphenols from fresh grape powder directly affect macrophage atherogenicity by reducing macrophage-mediated oxidation of LDL and cellular uptake of oxidized LDL. Both of these processes can eventually reduce macrophage cholesterol accumulation and foam cell formation and hence attenuate atherosclerosis development.

Animals↗
PubMed2005

Molecular analysis of cardiomyocytes derived from human embryonic stem cells.

During early embryogenesis, the cardiovascular system is the first system to be established and is initiated by a process involving the hypoblastic cells of the primitive endoderm. Human embryonic stem (hES) cells provide a model to investigate the early developmental stages of this system. When removed from their feeder layer, hESC create embryoid bodies (EB) which, when plated, develop areas of beating cells in 21.5% of the EB. These spontaneously contracting cells were demonstrated using histology, immunostaining and reverse transcription-polymerase chain reaction (RT-PCR), to possess morphological and molecular characteristics consistent with cardiomyocytic phenotypes. In addition, the expression pattern of specific cardiomyocytic genes in human EB (hEB) was demonstrated and analyzed for the first time. GATA-4 is the first gene to be expressed in 6-day-old EB. Alpha cardiac actin and atrial natriuretic factor are expressed in older hEB at 10 and 20 days, respectively. Light chain ventricular myosin (MLC-2V) was expressed only in EB with beating areas and its expression increased with time. Alpha heavy chain myosin (alpha-MHC) expression declined in the pulsating hEB with time, in contrast to events in EB derived from mice. We conclude that human embryonic stem cells can provide a useful tool for research on embryogenesis in general and cardiovascular development in particular.

Biomarkers↗
PubMed2004

Vascular development in early human embryos and in teratomas derived from human embryonic stem cells.

During early human embryonic development, blood vessels are stimulated to grow, branch, and invade developing tissues and organs. Pluripotent human embryonic stem cells (hESCs) are endowed with the capacity to differentiate into cells of blood and lymphatic vessels. The present study aimed to follow vasculogenesis during the early stages of developing human vasculature and to examine whether human neovasculogenesis within teratomas generated in SCID mice from hESCs follows a similar course and can be used as a model for the development of human vasculature. Markers and gene profiling of smooth muscle cells and endothelial cells of blood and lymphatic vessels were used to follow neovasculogenesis and lymphangiogenesis in early developing human embryos (4-8 weeks) and in teratomas generated from hESCs. The involvement of vascular smooth muscle cells in the early stages of developing human embryonic blood vessels is demonstrated, as well as the remodeling kinetics of the developing human embryonic blood and lymphatic vasculature. In teratomas, human vascular cells were demonstrated to be associated with developing blood vessels. Processes of intensive remodeling of blood vessels during the early stages of human development are indicated by the upregulation of angiogenic factors and specific structural proteins. At the same time, evidence for lymphatic sprouting and moderate activation of lymphangiogenesis is demonstrated during these developmental stages. In the teratomas induced by hESCs, human angiogenesis and lymphangiogenesis are relatively insignificant. The main source of blood vessels developing within the teratomas is provided by the murine host. We conclude that the teratoma model has only limited value as a model to study human neovasculogenesis and that other in vitro methods for spontaneous and guided differentiation of hESCs may prove more useful.

Animals↗
PubMed2004

Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone.

BACKGROUND: The renin-angiotensin-aldosterone system is involved in the pathogenesis of atherosclerosis, partially because of its pro-oxidative properties. We questioned the effect and mechanisms of action of administration of aldosterone to apolipoprotein E-deficient (E(0)) mice on their macrophages and aorta oxidative status and the ability of pharmacological agents to block this effect. METHODS AND RESULTS: Aldosterone (0.2 to 6 microg. mouse(-1) x d(-1)) was administered to E(0) mice alone or in combination with eplerenone (200 mg x kg(-1) x d(-1)), ramipril (5 mg x kg(-1) x d(-1)), or losartan (25 mg x kg(-1) x d(-1)). Mouse aortic atherosclerotic lesion area and macrophage and aortic oxidative status were evaluated. Aldosterone administration enhanced the mouse atherosclerotic lesion area by 32%. Mouse peritoneal macrophages and aortic segments from aldosterone-treated mice exhibited increased superoxide anion formation by up to 155% and 69%, respectively, and this effect was probably mediated by NADPH oxidase activation, because increased translocation of its cytosolic component p47phox to the macrophage plasma membrane was observed. THP-1 macrophages incubated in vitro with aldosterone (10 micromol/L) exhibited a higher capacity to release superoxide ions by 110% and increased ability to oxidize LDL by 74% compared with control cells. Aldosterone administration enhanced mouse peritoneal macrophage ACE activity and mRNA expression by 2.3-fold and 2.4-fold, respectively. Only cotreatment of eplerenone with ramipril or losartan completely blocked the oxidative effects of aldosterone. CONCLUSIONS: Aldosterone administration to E(0) mice increased macrophage oxidative stress and atherosclerotic lesion development. Blocking of the mineralocorticoid receptor and inhibition of tissue ACE and/or the angiotensin receptor-1 reduced aldosterone deleterious pro-oxidative and proatherogenic effects.

Aldosterone↗
PubMed2004

Handgrip strength as a diagnostic tool in work-related upper extremity musculoskeletal disorders in women.

The aim of this study was to determine if handgrip strength might be used as a diagnostic tool in musculoskeletal disorders of the upper extremities in women working in an industrial environment. The setting was an electronic factory with four groups of women (n = 101) in a factory assembling electronic components. Handgrip strength was measured using a Jamar hydraulic hand dynamometer. The study investigated grip strength in managers-engineers, cable wiring, circuit board assembly, integrated circuits women at 90 degrees elbow flexion and 180 elbow extension. Women seeking or receiving medical care for musculoskeletal disorders of the upper extremities or neck showed significant declines (p < 0.01) in handgrip strength and these also related to the type of work and the level of perceived physical exertion. Women in the managerial-engineering group showed fewer musculoskeletal disorders of the upper extremity compared with the other groups and also had significantly stronger handgrip. Our findings encourage us to recommend hand dynamometer testing as a useful diagnostic tool to determine loss of handgrip strength.

Adult↗
PubMed2004

Matrix metalloproteinases and skeletal muscle: a brief review.

Matrix metalloproteinases (MMPs) are a family of zinc- dependent proteolytic enzymes that function mainly in the extracellular matrix, where they contribute to the development, functioning, and pathology of a wide range of tissues. This mini-review describes the MMPs and tissue inhibitors of MMPs (TIMPs) in skeletal muscle, and considers their involvement in muscle development, ischemia, myonecrosis, angiogenesis, denervation, exercise-induced injuries, disuse atrophy, muscle repair and regeneration, and inflammatory myopathies and dystrophies. Despite the very limited information currently available on MMPs and their inhibitors in skeletal muscle, it is becoming increasingly clear that they have important physiological functions in maintenance of the integrity and homeostasis of muscle fibers and of the extracellular matrix. Understanding the roles of MMPs and TIMPs may lead to the development of new drug-related treatments for various muscle disorders based on suppression or upregulation of their expression.

Animals↗