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Biomedical subjects

Joseph Boyle

Publications and source records attributed to Joseph Boyle.

8 recordsLinked to original sources

Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes.

Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is important for neutrophil transmigration and activation, can be degraded by S. pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8 than throat isolates. Degradation of IL-8 was the result of a single specific cleavage between 59glutamine and 60arginine within the IL-8 C-terminal alpha helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving activity was found in partially purified supernatant of a necrotizing fasciitis isolate, and this activity was associated with an approximately 150-kDa fraction containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by S. pyogenes represents an unprecedented mechanism of immune evasion, effectively preventing IL-8 C-terminus-mediated endothelial translocation and subsequent recruitment of neutrophils.

Amino Acid Sequence↗

Dissection of BXSB lupus phenotype using mice congenic for chromosome 1 demonstrates that separate intervals direct different aspects of disease.

To dissect the individual effects of the four non-MHC, autosomal loci (Bxs1 to Bxs4) that contribute to SLE susceptibility in BXSB mice, we generated congenic lines from chromosome 1 on a C57BL/10.Y(BXSB) (B10.Yaa) background for the intervals (values in megabases (Mb)) Bxs1 (46.3-89.2 Mb), Bxs1/4 (20.0-65.9 Mb), Bxs1/2 (64.4-159.0 Mb), and Bxs2/3 (105.4-189.0 Mb). Glomerulonephritis, qualitatively similar to that seen in the parental BXSB strain, developed in three of these congenic strains. Early onset, severe disease was observed in B10.Yaa.BXSB-Bxs2/3 congenic mice and caused 50% mortality by 12 mo. In B10.Yaa.BXSB-Bxs1/4 mice disease progressed more slowly, resulting in 13% mortality at 12 mo. The progression of renal disease in both of these strains was correlated with the level of anti-dsDNA Abs. B10.Yaa.BXSB-Bxs1 mice, despite their genetic similarity to B10.Yaa.BXSB-Bxs1/4 mice, developed a low-grade glomerulonephritis in the absence of anti-dsDNA Abs. Thus, Bxs4 directed an increase in titer and spectrum of autoantibodies, whereas Bxs1 promoted the development of nephritis. The Bxs2 interval was linked to the production of anti-dsDNA Abs without concomitant glomerulonephritis. In contrast, the Bxs3 interval was sufficient to generate classic lupus nephritis in a nonautoimmune-prone strain. Immune phenotype differed between controls and congenics with a significant increase in B220(+) cells in BXSB and B10.Yaa.BXSB-Bxs2/3, and an increase in CD4 to CD8 ratio in both BXSB and B10.Yaa.BXSB-Bxs1/4. Disease in the Bxs3 mice was delayed in comparison to the BXSB parental strain, emphasizing the necessity for multiple interactions in the production of the full BXSB phenotype.

Animals↗

Medical ethics and double effect: the case of terminal sedation.

The use of terminal sedation to control the intense discomfort of dying patients appears both to be an established practice in palliative care and to run counter to the moral and legal norm that forbids health care professionals from intentionally killing patients. This raises the worry that the requirements of established palliative care are incompatible with moral and legal opposition to euthanasia. This paper explains how the doctrine of double effect can be relied on to distinguish terminal sedation from euthanasia. The doctrine of double effect is rooted in Catholic moral casuistry, but its application in law and morality need not depend on the particular framework in which it was developed. The paper further explains how the moral weight of the distinction between intended harms and merely foreseen harms in the doctrine of double effect can be justified by appeal to a limitation on the human capacity to pursue good.

Casuistry↗

Catholic social justice and health care entitlement packages.

This paper explores the implications of Roman Catholic teachings on social justice and rights to health care. It argues that contemporary societies, such as those in North America and Western Europe, have an obligation to provide health care to their citizens as a matter of right. Moral considerations provide a basis for evaluating concerns about the role of equality when determining health care entitlements and giving some precision to the widespread belief that the right to health care requires equal entitlement to health care benefits.

Catholicism↗

Further thoughts on double effect: some preliminary responses.

Since the papers in this issue by Alan Donagan, Don Marquis, William Nelson and Warren Quinn raise complex and challenging questions about almost every aspect of my "Who is Entitled to Double Effect", I cannot, in the present context, provide more than preliminary responses to some of the more important issues they raise in the hope that this might contribute to further clarification of the doctrine of double effect (DDE).

Bioethical Issues↗