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Biomedical subjects

William Foster

Publications and source records attributed to William Foster.

14 recordsLinked to original sources
PubMed2006

Inhibited skeletal muscle healing in cyclooxygenase-2 gene-deficient mice: the role of PGE2 and PGF2alpha.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat skeletal muscle injury. However, studies have shown that NSAIDs may be detrimental to the healing process. Mediated by prostaglandin F(2alpha) (PGF(2alpha)) and prostaglandin E(2) (PGE(2)), the cycloxygenase-2 (COX-2) pathway plays an important role in muscle healing. We hypothesize that the COX-2 pathway is important for the fusion of muscle cells and the regeneration of injured muscle. For the in vitro experiments, we isolated myogenic precursor cells from wild-type (Wt) and COX-2 gene-deficient (COX-2(-/-)) mice and examined the effect of PGE(2) and PGF(2alpha) on cell fusion. For the in vivo experiments, we created laceration injury on the tibialis anterior (TA) muscles of Wt and COX-2(-/-) mice. Five and 14 days after injury, we examined the TA muscles histologically and functionally. We found that the secondary fusion between nascent myotubes and myogenic precursor cells isolated from COX-2(-/-) mice was severely compromised compared with that of Wt controls but was restored by the addition of PGF(2alpha) or, to a lesser extent, PGE(2) to the culture. Histological and functional assessments of the TA muscles in COX-2(-/-) mice revealed decreased regeneration relative to that observed in the Wt mice. The findings reported here demonstrate that the COX-2 pathway plays an important role in muscle healing and that prostaglandins are key mediators of the COX-2 pathway. It suggests that the decision to use NSAIDs to treat muscle injuries warrants critical evaluation because NSAIDs might impair muscle healing by inhibiting the fusion of myogenic precursor cells.

Animals↗
PubMed2005

Distinct gene expression profiles in adult mouse heart following targeted MAP kinase activation.

Three major MAP kinase signaling cascades, ERK, p38, and JNK, play significant roles in the development of cardiac hypertrophy and heart failure in response to external stress and neural/hormonal stimuli. To study the specific function of each MAP kinase branch in adult heart, we have generated three transgenic mouse models with cardiac-specific and temporally regulated expression of activated mutants of Ras, MAP kinase kinase (MKK)3, and MKK7, which are selective upstream activators for ERK, p38, and JNK, respectively. Gene expression profiles in transgenic adult hearts were determined using cDNA microarrays at both early (4-7 days) and late (2-4 wk) time points following transgene induction. From this study, we revealed common changes in gene expression among the three models, particularly involving extracellular matrix remodeling. However, distinct expression patterns characteristic for each pathway were also identified in cell signaling, growth, and physiology. In addition, genes with dynamic expression differences between early vs. late stages illustrated primary vs. secondary changes on MAP kinase activation in adult hearts. These results provide an overview to both short-term and long-term effects of MAP kinase activation in heart and support some common as well as unique roles for each MAP kinase cascade in the development of heart failure.

Animals↗
PubMed2005

The use of suramin, an antifibrotic agent, to improve muscle recovery after strain injury.

BACKGROUND: Muscle strain injuries are extremely common in sports medicine. Muscle healing often is hindered by scar tissue formation after injury. HYPOTHESIS: Suramin can prevent scar tissue formation and improve muscle healing after injury because of its ability to antagonize transforming growth factor-beta1, a fibrotic cytokine. STUDY DESIGN: Controlled laboratory study. MATERIALS AND METHODS: In vitro, muscle-derived fibroblasts (a potential cell source of muscle fibrosis) were incubated with suramin and/or transforming growth factor-beta1; a cell growth curve was obtained. In vivo, mouse gastrocnemius muscles were strain injured. Suramin or sham/control intramuscular injections were performed after injury at various time points. Mice were sacrificed at various time points after injury, and skeletal muscle tissue was evaluated by using histological and physiological tests. Statistical analysis was performed by using analysis of variance and Fisher tests. RESULTS: Suramin decreased the stimulating effect of transforming growth factor-beta1 on the growth of muscle-derived fibroblasts in vitro. Significantly less fibrous scar formation was observed in suramin-treated muscles than in sham-injected muscles. The fast-twitch and tetanus strength of suramin-treated muscles was also significantly greater relative to that of control muscles. CONCLUSIONS: Suramin blocked the stimulatory effect of transforming growth factor-beta1 on muscle-derived fibroblasts in vitro. Suramin also reduced fibrous scar formation in muscle and enhanced muscle strength in strain-injured skeletal muscle. CLINICAL RELEVANCE: These results may facilitate the development of strategies to enhance muscle healing after injury.

Animals↗
PubMed2005

Should nonprofits seek profits?

Twenty years ago, it would have been shocking for a children's choir to sell singing telegrams or for an organization serving the homeless to dabble in property management. Today, it seems routine. Nonprofits increasingly feel compelled to launch earned-income ventures--not only to appear more disciplined and businesslike to stakeholders but also to reduce their reliance on fundraising. There's plenty of hype about the value of earned-income ventures in the nonprofit world, but such projects account for only a small share offunding in most nonprofit domains, and few of the ventures make money. Moreover, when the authors examined how nonprofits evaluate potential enterprises, they discovered a pattern of unwarranted optimism. The potential financial returns are often exaggerated, and the challenges of running a successful business are routinely discounted. But the biggest downside of such ventures is that they can distract nonprofits' managers from their core social missions and, in some cases, even subvert those missions. There are several reasons for the gap between the hype and the reality. One is that an organization's nonfinancial concerns-such as a desire to hire the disadvantaged-can hamper it in the commercial marketplace. Another is that nonprofits' executives tend to overlook the distinction between revenue and profit. For example, a youth services organization that had received funding to launch a food products enterprise hired young people and began making salad dressing. The nonprofit believed it spent $3.15 to produce each bottle of dressing that was sold for $3.50. But when expenses such as unused ingredients and managers' salaries were factored in, the cost per bottle reached a staggering $90. Earned-income ventures do have a role in the nonprofit sector, the authors say, but unrealistic expectations are distorting managers' decisions, wasting precious resources, and leaving important social needs unmet.

Charities↗
PubMed2004

Circulating endothelial cells, von Willebrand factor, interleukin-6, and prognosis in patients with acute coronary syndromes.

Markers of inflammation (eg, interleukin-6 [IL-6]), and endothelial perturbation (von Willebrand factor [VWF], circulating endothelial cells [CECs]) are altered in acute coronary syndromes (ACS). We hypothesized that CECs and IL-6 levels during the first 48 hours of ACS would predict 30-day and 1-year major cardiovascular end points (MACE). A total of 156 patients with ACS were included. Blood was drawn on admission (baseline) and 48 hours later for plasma VWF, IL-6 (both enzyme-linked immunosorbent assay [ELISA]), and CECs (CD146 immunomagnetic separation). CEC phenotyping was performed by indirect immunoperoxidase staining. At 30 days, 48 patients had a MACE, a predicted by baseline and 48-hour CECs and IL-6 levels, 48-hour VWF levels, and by the "admission-48 hour change" (Delta) in CECs, VWF, and IL-6 (all P = .002). On multivariate analysis, 48-hour CECs (P < .001) were the strongest predictor of MACE, followed by DeltaIL-6 (P = .01) and DeltaVWF (P = .048); 48-hour CECs were the only predictor of death (P = .007). At 1 year, 65 patients had MACE, predicted by 48-hour CECs and DeltaIL-6 levels (P < .001); age (P = .046) and 48-hour CECs (P < .001) were the only predictors of death. CECs stained 93% positive for endothelial nitric oxide synthase (eNOS) but were less than 1% positive for CD34, CD36, and CD45 and less than 3% for CD31. Like raised VWF, abnormal CECs and IL-6 levels during the first 48 hours of ACS were strongly associated with 30-day MACE. CECs at 48 hours were the only independent predictor of both death and MACE at 30 days and 1 year, indicating the crucial role of endothelial/vascular damage in ACS pathophysiology.

Acute Disease↗
PubMed2004

Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis.

Transforming growth factor-beta1 (TGF-beta1) is thought to play a crucial role in fibrotic diseases. This study demonstrates for the first time that TGF-beta1 stimulation can induce myoblasts (C2C12 cells) to express TGF-beta1 in an autocrine manner, down-regulate the expression of myogenic proteins, and initiate the production of fibrosis-related proteins in vitro. Direct injection of human recombinant TGF-beta1 into skeletal muscle in vivo stimulated myogenic cells, including myofibers, to express TGF-beta1 and induced scar tissue formation within the injected area. We also observed the local expression of this growth factor by myogenic cells, including regenerating myofibers, in injured skeletal muscle. Finally, we demonstrated that TGF-beta1 gene-transfected myoblasts (CT cells) can differentiate into myofibroblastic cells after intramuscular transplantation, but that decorin, an anti-fibrosis agent, prevents this differentiation process by blocking TGF-beta1. In summary, these findings indicate that TGF-beta1 is a major stimulator that plays a significant role in both the initiation of fibrotic cascades in skeletal muscle and the induction of myogenic cells to differentiate into myofibroblastic cells in injured muscle.

Animals↗
PubMed2003

Antifibrotic effects of suramin in injured skeletal muscle after laceration.

Muscle injuries are very common in traumatology and sports medicine. Although muscle tissue can regenerate postinjury, the healing process is slow and often incomplete; complete recovery after skeletal muscle injury is hindered by fibrosis. Our studies have shown that decreased fibrosis could improve muscle healing. Suramin has been found to inhibit transforming growth factor (TGF)-beta1 expression by competitively binding to the growth factor receptor. We conducted a series of tests to determine the antifibrotic effects of suramin on muscle laceration injuries. Our results demonstrate that suramin (50 microg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (alpha-smooth muscle actin) in vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle regeneration, which led to efficient functional muscle recovery. These results support our hypothesis that prevention of fibrosis could enhance muscle regeneration, thereby facilitating more efficient muscle healing. This study could significantly contribute to the development of strategies to promote efficient muscle healing and functional recovery.

3T3 Cells↗
PubMed2003

Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis.

Skeletal muscle is able to repair itself through regeneration. However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis. Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated. Previously, we have determined that insulin-like growth factor-1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient healing and recovery of strength after muscle injuries. Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis. This improvement was not associated with improved responses to physiological testing, at least at the time-points tested in this study.

Animals↗
PubMed2003

Gamma interferon as an antifibrosis agent in skeletal muscle.

Muscle injuries are a common problem in sports medicine. Skeletal muscle can regenerate itself, but the process is both slow and incomplete. Previously we and others have used growth factors to improve the regeneration of muscle, but the muscle healing was impeded by scar tissue formation. However, when we blocked the fibrosis process with decorin, an antifibrosis agent, we improved the muscle healing. Here we show that gammainterferon (gammaINF)--a cytokine that inhibits the signaling of transforming growth factor beta1 (TGFbeta1), a fibrotic stimulator--reduces fibrosis formation and improves the healing of lacerated skeletal muscle. With gammaINF treatment, the growth rate of muscle-derived fibroblasts was reduced and the level of fibrotic protein expression induced by TGFbeta1 (including TGFbeta1, vimentin, and alpha-smooth muscle actin) was down-regulated in vitro. In a mouse laceration model, the area of fibrosis decreased when gammaINF was injected at either 1 or 2 weeks after injury. More importantly, the injection of gammaINF at either 1 or 2 weeks post-injury was found to improve muscle function in terms of both fast-twitch and tetanic strength. This study demonstrates that gammaINF is a potent antifibrosis agent that can improve muscle healing after laceration injury.

Animals↗
PubMed2002

How aphids lose their marbles.

Insects provide examples of many cunning stratagems to cope with the challenges of living in a world dominated by surface forces. Despite being the current masters of the land environment, they are at constant risk of being entrapped in liquids, which they prevent by having waxy and hairy surfaces. The problem is particularly acute in an enclosed space, such as a plant gall. Using secreted wax to efficiently parcel and transport their own excrement, aphids were able to solve this problem 200 Myr ago. Here, we report on the physical and physiological significance of this ingenious solution. The secreted powdery wax has three distinct roles: (i) it is hydrophobic, (ii) it creates a microscopically rough inner gall surface made of weakly compacted wax needles making the gall ultra-hydrophobic, and (iii) it coats the honeydew droplets converting them into liquid marbles, that can be rapidly and efficiently moved.

Animals↗
PubMed2002

High reproductive skew in tropical hover wasps.

A plethora of recent models examines how genetic and environmental factors might influence partitioning of reproduction ('skew') in animal societies, but empirical data are sparse. We used three microsatellite loci to estimate skew on 13 nests of the Malaysian hover wasp, Liostenogaster flavolineata. Groups are small in L. flavolineata (1-10 females) and all females are capable of mating and laying eggs. Despite considerable variation between nests in parameters expected to influence skew, skew was uniformly high. On 11 of the 13 nests, all female eggs had been laid by a single dominant female. A second female had laid one to two out of 5-10 eggs respectively on the two remaining nests. A likelihood analysis suggested that on average, 90% of the male eggs had also been laid by the dominant. The slightly lower skew among male eggs might reflect the lower average relatedness of subordinates to male versus female offspring of the dominant. We suggest that high skew in L. flavolineata may result from strong ecological constraints and a relatively high probability that a subordinate will eventually inherit the dominant, egg-laying position.

Animals↗