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Biomedical subjects

Kevin Connolly

Publications and source records attributed to Kevin Connolly.

5 recordsLinked to original sources
PubMed2004

Conservation and divergence of the genetic structure of larval foraging behaviour in two species of the Drosophila simulans clade.

Larvae of the sibling species Drosophila simulans and D. mauritiana have rates of locomotor and feeding activity that are closely similar. Comparisons of the trait means for intra- and interspecific hybrids show that significant epistatic interactions affect both characters when the genomes of the two species are combined. The phenotypic variances of progenies obtained by backcrossing the interspecific hybrids to their respective parent species show that appreciable genetic turnover affecting foraging behaviour has occurred since their two phylogenetic lines diverged.

Analysis of Variance↗
PubMed2003

Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect.

Graft-versus-host disease (GVHD) is the principal complication after allogeneic bone marrow transplantation (BMT). Reductions in systemic GVHD are frequently associated with a corresponding diminishment of the graft-versus-leukemia (GVL) response. In this study, we tested the effects of a novel recombinant human keratinocyte growth factor, repifermin (keratinocyte growth factor-2), on the induction of GVHD in a well-defined murine BMT model (B6 --> B6D2F1). Administration of repifermin (5 mg/kg/d) to allogeneic BMT recipients resulted in a significant decrease in both systemic GVHD and target organ histopathology. Repifermin treatment also reduced serum levels of tumor necrosis factor alpha and lipopolysaccharide compared with control mice. In contrast, repifermin did not affect T-cell proliferation, cytokine production, or cytotoxic responses to host antigens. When 2000 host-derived P815 (H-2(d)) leukemia cells were added to the bone marrow inoculum, repifermin preserved GVL effects and resulted in significantly delayed mortality compared with control-treated allogeneic BMT recipients. Collectively, these data suggest that repifermin administration may represent a novel strategy to separate the toxicity of GVHD from the beneficial GVL effects after allogeneic BMT.

Animals↗
PubMed2002

In vitro and in vivo effects of repifermin (keratinocyte growth factor-2, KGF-2) on human carcinoma cells.

PURPOSE: Repifermin (keratinocyte growth factor-2, KGF-2) is a growth factor that selectively induces epithelial cell proliferation, differentiation and migration. The objective of this study was to assess the effect of repifermin on in vitro tumor cell proliferation and in vivo tumor growth using a variety of human carcinoma cell lines with differing growth rates and levels of KGF receptor (KGFR) expression. METHODS: Potential effects of repifermin on in vitro cell proliferation were evaluated by alamarBlue and/or [(3)H]-thymidine incorporation assays under a range of serum conditions. In vivo tumor growth was evaluated by implanting KGFR(+) carcinomas subcutaneously into nude mice and measuring tumor growth over time in mice injected intravenously (i.v.) or intraperitoneally (i.p.) with repifermin or placebo. RESULTS: In vitro, none of the 30 human carcinoma cell lines tested demonstrated a substantial increase in proliferation in response to repifermin over the concentration range 0.01 to 1000 ng/ml. In vivo results showed no significant tumor growth-promoting activity when single- or multiple-cycle intravenous injections of repifermin (1 mg/kg) were given to athymic nude mice inoculated with human KGFR(+) tumors of the pharynx (Detroit 562, FaDu), colon (Caco-2), salivary gland (A-253) or tongue (SCC-25, CAL 27). In addition, repifermin (0.2 or 2 mg/kg) injected i.p. for 2 weeks had no effect on the growth of eight other human carcinomas including those of the ovary (NIH:OVCAR-3, SK-OV 3, PA-1), bladder (SCaBER), epidermis (A 431), lung (SW 900), breast (MDA-MB-231) and cervix (SiHa). CONCLUSIONS: Repifermin had no in vitro or in vivo proliferative effects on KGFR(+) human epithelial-like tumors. This failure to stimulate tumor cell growth highlights the ability of repifermin to specifically target normal epithelial tissue. This is critical to the safety profile of repifermin, since it is currently in phase II clinical trials for the treatment of cancer patients with mucositis resulting from chemo- or radiotherapy.

Animals↗
PubMed2002

Domain-specific and generalized disgust sensitivity in blood-injection-injury phobia: the application of behavioral approach/avoidance tasks.

The separate and combined roles of fear and disgust in mediating phobic responding in blood-injection-injury (BII) phobia have generated considerable empirical interest. The present study aimed to replicate previous research regarding fear and disgust responding to phobia-relevant and generalized disgust elicitors, as well as to provide a novel examination of performance on behavioral approach/avoidance tasks (BATs) and the "contaminated cookie" procedure (i.e., willingness to eat a cookie after it has come into brief contact with a threat-relevant stimulus). Fear and disgust responses toward pictures (mutilation, insects) and in vivo stimuli (bloody gauze, severed deer leg, cockroach, worm) were assessed in a sample of analogue BII phobics and nonphobics. Consistent with previous research. BII phobics expressed significantly greater fear and disgust toward phobia-relevant pictures and BAT stimuli, with disgust being the dominant emotional response. We failed to find any between-group differences on disgust responding toward the generalized disgust pictures and BAT stimuli. Results from the BATs suggest that BII phobics were less willing to perform all tasks involving blood stimuli, and less willing to complete the latter stages of the insect BATs. BII phobics were less likely to eat the "contaminated cookie" after it had come into contact with only the insect stimuli. Future implications for research examining domain-specific and generalized disgust sensitivity in BII phobia are outlined.

Analysis of Variance↗