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Biomedical subjects

Catherine S Williams

Publications and source records attributed to Catherine S Williams.

11 recordsLinked to original sources
PubMed2006

Host species barriers to influenza virus infections.

Most emerging infectious diseases in humans originate from animal reservoirs; to contain and eradicate these diseases we need to understand how and why some pathogens become capable of crossing host species barriers. Influenza virus illustrates the interaction of factors that limit the transmission and subsequent establishment of an infection in a novel host species. Influenza species barriers can be categorized into virus-host interactions occurring within individuals and host-host interactions, either within or between species, that affect transmission between individuals. Viral evolution can help surmount species barriers, principally by affecting virus-host interactions; however, evolving the capability for sustained transmission in a new host species represents a major adaptive challenge because the number of mutations required is often large.

Animals↗
PubMed2005

Epidermal growth factor reduces hepatic sequelae in experimental necrotizing enterocolitis.

BACKGROUND AND AIM: Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We recently demonstrated that the gut/liver axis plays an important role in the pathophysiology of NEC through the release of inflammatory mediators into the intestinal lumen. We have also shown that supplementation of formula with epidermal growth factor (EGF) dramatically decreases ileal pathology associated with experimental NEC. In this study, we examined the effects of EGF on the liver portion of the gut/liver axis in the neonatal rat model of NEC. METHODS: Newborn rats were divided into three experimental groups, NEC, hand-fed with growth-factor free formula; NEC + EGF, hand-fed with formula supplemented with 500 ng/ml rat EGF; or DF, dam fed. All animals were exposed to asphyxia and cold stress twice daily for 4 days to develop NEC. RESULTS: EGF receptor expression was significantly (p <or= 0.01) decreased in the NEC+EGF group compared to the NEC group. EGF supplementation significantly decreased Kupffer cell numbers (p <or= 0.01) as well as hepatic tumor necrosis factor (TNF)-alpha and interleukin-18 production (p <or= 0.05). Further, TNF-alpha in the intestinal luminal contents of the NEC+EGF group were normalized to levels observed in DF controls compared to the NEC group (p <or= 0.05). Activated nuclear factor-kappaB was also substantially decreased in the NEC+EGF group versus the NEC group. CONCLUSION: The results of this study indicate that EGF normalizes cytokine overproduction in the liver of neonatal rats with NEC, which contributes to diminished intestinal damage during the development of experimental NEC. These data suggest that supplementation of formula with EGF can have beneficial effects on the gut/liver axis during NEC pathogenesis.

Animals↗
PubMed2004

Epidermal growth factor reduces intestinal apoptosis in an experimental model of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although end-stage NEC is characterized histopathologically as extensive necrosis, apoptosis may account for the initial loss of epithelium before full development of disease. We have previously shown that epidermal growth factor (EGF) reduces the incidence of NEC in a rat model. Although EGF has been shown to protect intestinal enterocytes from apoptosis, the mechanism of EGF-mediated protection against NEC is not known. The aim of this study was to investigate if EGF treatment elicits changes in expression of apoptotic markers in the ileum during the development of NEC. With the use of a well-established neonatal rat model of NEC, rats were divided into the following three experimental groups: dam fed (DF), milk formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC+EGF). Changes in ileal morphology, gene and protein expression, and histological localization of apoptotic regulators were evaluated. Anti-apoptotic Bcl-2 mRNA levels were markedly reduced and pro-apoptotic Bax mRNA levels were markedly elevated in the NEC group compared with DF controls. Supplementation of EGF into formula significantly increased anti-apoptotic Bcl-2 mRNA, whereas pro-apoptotic Bax was significantly decreased. The Bax-to-Bcl-2 ratio for mRNA and protein was markedly decreased in NEC+EGF animals compared with the NEC group. The presence of caspase-3-positive epithelial cells was markedly reduced in EGF-treated rats. These data suggest that alteration of the balance between pro-and anti-apoptotic proteins in the site of injury is a possible mechanism by which EGF maintains intestinal integrity and protects intestinal epithelium against NEC injury.

Animals↗
PubMed2003

Increased epidermal growth factor levels in human milk of mothers with extremely premature infants.

Maternal milk is the major source of nutrients and growth-promoting substances in the first weeks of life for the majority of neonates. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are trophic peptides present in human milk with significant healing effects on injured gastrointestinal mucosa. Decreasing gestational age of neonates is associated with higher risk of developing gastrointestinal disorders, and human milk provides better protection against these diseases compared with formula. The aim of this study was to evaluate the concentrations of EGF and TGF-alpha in human milk collected from mothers with infants born: extremely preterm, preterm, and full term. Milk samples were collected at the end of first, second, and fourth week postpartum from each mother of infants born in one of the three gestational age groups: extremely preterm (23-27 wk, n = 16), preterm (32-36 wk, n = 16), and full term (38-42 wk, n = 15). Milk concentrations of EGF and TGF-alpha were quantified with a homologous RIA in the milk aqueous fraction. Concentrations of EGF in human milk from the extremely preterm group (23-27 wk) were significantly higher compared with values from the preterm and full-term groups throughout the first month of lactation. A similar pattern was observed with human milk TGF-alpha; however, milk TGF-alpha levels were lower than EGF. In conclusion, we have found higher concentrations of EGF and TGF-alpha in human milk of mothers with extremely preterm babies. These data may indicate the potential importance of milk-borne EGF and TGF-alpha for the development of extremely premature infants.

Adult↗
PubMed2003

Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Along with pathological effects in the ileum, severe NEC is often accompanied by multisystem organ failure, including liver failure. The aim of this study was to determine the changes in hepatic cytokines and inflammatory mediators in experimental NEC. The well-established neonatal rat model of NEC was used in this study, and changes in liver morphology, numbers of Kupffer cells (KC), gene expression, and histological localization of IL-18, TNF-alpha, and inducible nitric oxide synthase were evaluated. Intestinal luminal TNF-alpha levels were also measured. Production of hepatic IL-18 and TNF-alpha and numbers of KC were increased in rats with NEC and correlated with the progression of intestinal damage during NEC development. Furthermore, increased levels of TNF-alpha in the intestinal lumen of rats with NEC was significantly decreased when KC were inhibited with gadolinium chloride. These results suggest an important role of the liver and the gut-liver axis in NEC pathogenesis.

Animals↗
PubMed2003

Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We have shown in previous studies that proinflammatory interleukin-18 and interleukin-12 are up-regulated in the ileum of rats with experimental NEC and that epidermal growth factor (EGF) reduces the development of disease. Here we investigated whether the protective effects of EGF are a result of changes in ileal interleukin-18, interleukin-12 and/or antiinflammatory interleukin-10. METHODS: Newborn rats were artificially fed with either growth-factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/mL EGF (RMS + EGF) and NEC was induced via exposure to asphyxia and cold stress. Cytokine expression and localization were assessed using reverse-transcription real-time polymerase chain reaction and immunohistology/confocal microscopy. RESULTS: Enteral administration of EGF (RMS + EGF) decreased overproduction of interleukin-18 and increased interleukin-10 production in the ileum. Furthermore, increased interleukin-10 production was associated with up-regulation of the transcription factor Sp1 in RMS + EGF rats. CONCLUSIONS: These data suggest that EGF may reduce NEC via increased interleukin-10 and decreased interleukin-18 and that EGF-mediated up-regulation of Sp1 may account for the increased interleukin-10.

Animals↗
PubMed2003

Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL-10 in a neonatal rat model.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Maternal milk has been suggested to be partially protective against NEC; however, the mechanisms of this protection are not defined. The aim of this study was to examine the effect(s) of artificial feeding of rat milk (RM)-versus cow milk-based rat milk substitute (RMS) on the development of NEC in a neonatal rat model and elucidate the role of inflammatory cytokines in NEC pathogenesis. Newborn rats were artificially fed with either collected RM or RMS. Experimental NEC was induced by exposure to asphyxia and cold stress and evaluated by histologic scoring of damage in ileum. Intestinal cytokine mRNA expression was determined by real-time PCR. Cytokine histologic localization was performed by confocal microscopy. Similar to human NEC, artificial feeding of RM reduces the incidence and severity of NEC injury in neonatal rats. Freezing and thawing of collected RM did not eliminate the protective effect of maternal milk. Ileal IL-10 expression was significantly increased in the RM group compared with RMS. Increased IL-10 peptide production was detected in the RM group with signal localized predominantly in the cytoplasm of villus epithelial cells. These results suggest that the protective effect of maternal milk is associated with increased production of anti-inflammatory IL-10 in the site of injury. Better understanding of the mechanisms underlying these protective effects could be beneficial either in the prevention of NEC or in the development of future therapeutic strategies to cure NEC.

Animals↗
PubMed2002

Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of prematurely born infants. Maternal milk plays an important protective role against NEC development and is the major source of epidermal growth factor (EGF) for neonates. The aim of this study was to examine the effect of orally administered EGF on the incidence of NEC in a neonatal rat model. Newborn rats were artificially fed either with growth factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/ml of EGF (RMS+EGF). Experimental NEC was induced by exposure to asphyxia and cold stress. Development of NEC was evaluated by gross and histological scoring of damage in the ileum. Ileal EGF receptor (EGF-R), EGF, and transforming growth factor-alpha mRNA expression was assessed by RT competitive-PCR, and the EGF-R was localized by immunohistochemistry. EGF supplementation of formula reduced the incidence and severity of NEC in rats (13/16 RMS vs. 4/13 RMS+EGF). Ileal EGF-R mRNA expression was markedly increased in the RMS group compared with RMS+EGF. Enhanced EGF-R expression in the RMS group was localized predominantly in the epithelial cells of injured ileum. These data suggest a new potential therapeutic approach for the prevention and treatment of NEC.

Animals↗
PubMed2002

Up-regulation of IL-18 and IL-12 in the ileum of neonatal rats with necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Because the proinflammatory cytokines IL-18, IL-12, and interferon (IFN)-gamma have been implicated in other diseases of the small intestine, we hypothesized that these cytokines would play an important role in NEC pathogenesis. NEC was induced in newborn rats via enteral feeding with rat milk substitute and asphyxia and cold stress (RMS). Dam-fed, asphyxia- and cold-stressed littermates were used as controls (DF). After 96 h, the distal ileum was removed from all animals and processed to determine expression and localization of IL-18, IL-12, and IFN-gamma using real-time reverse transcriptase PCR and immunohistology. IL-18 and IL-12 mRNA from the RMS group were increased (p < or = 0.05) compared with DF controls, and there was a correlation between increasing IL-18 and IL-12 mRNA levels and progression of tissue damage (r = 0.629 and 0.588, respectively; p < or = 0.05). Immunohistology revealed IL-18 in the cytoplasm of villi and crypt enterocytes and IL-12-positive monocytes/macrophages were increased with disease progression (r = 0.503, p < or = 0.05). No differences in the number of IFN-gamma-positive cells were observed between groups. These data demonstrate up-regulation of IL-18 and IL-12 in experimental NEC and a correlation between production of these proinflammatory cytokines and progression of tissue damage.

Animals↗