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D Marquis

Publications and source records attributed to D Marquis.

13 recordsLinked to original sources
PubMed2002

A defence of the potential future of value theory.

In this issue of the journal Mark Brown has offered a new argument against my potential future of value theory. I argue that even though the premises of this new argument are far more defensible than the premises of his old argument, the new argument does not show that the potential future of value theory of the wrongness of killing is false. If the considerations to which Brown appeals are used, not to show that the potential future of value theory is false, but to show that abortion is morally permissible, they are also unsuccessful. I also argue that Brown's clarified self-represented future of value account and Simon Parsons's account of the wrongness of killing are both subject to major difficulties. Finally, I show, in an appendix, that Brown's assertion that my discussion of his views suffers from major logical errors is false.

Abortion, Legal↗
PubMed2001

Deprivations, futures and the wrongness of killing.

In my essay, Why abortion is immoral, I criticised discussions of the morality of abortion in which the crucial issue is whether fetuses are human beings or whether fetuses are persons. Both argument strategies are inadequate because they rely on indefensible assumptions. Why should being a human being or being a person make a moral difference? I argued that the correct account of the morality of abortion should be based upon a defensible account of why killing children and adults is wrong. I claimed that what makes killing us wrong is that our premature deaths deprive us of our futures of value, that is, the goods of life we would have experienced had we survived. This account of the wrongness of killing explains why killing is one of the worst of crimes and how killing greatly harms the victim. It coheres with the attitudes of those with cancer or HIV facing premature death. It explains why we believe it is wrong to kill infants (as personhood theories do not). It does not entail that it wrongs a human being to end her life if she is in persistent vegetative state or if her future must consist only of unbearable physical suffering and she wants to die (as sanctity of human life theories do not). This account of the wrongness of killing implies (with some defensible additional assumptions) that abortion is immoral because we were fetuses once and we know those fetuses had futures of value. Mark Brown claims that this potential future of value account is unsound because it implies that we have welfare rights to what we need to stay alive that most people would reject. I argue that Brown is incorrect in two ways: a welfare right to what we need to stay alive is not directly implied by my account and, in addition, most of us do believe that dependent human beings have substantial welfare rights to what they need to stay alive. Brown argues that depriving us of a future of value of which we have mental representations both is a better explanation of the wrongness of killing and does not imply that abortion is immoral. I reply that (a) if Brown's arguments against my view were sound, those arguments could be easily adapted to show that his view is unsound as well and (b) Brown's view is both ambiguous and unsound on any interpretation. The most popular class of pro-choice argument strategies appeals to the view that some or all fetuses lack either a mental state or function or a capacity for a mental state or function necessary for possession of the right to life. Desires, interests, sentience, various concepts, moral agency, and rationality have all been suggested as candidates for this crucial mental role. Brown's analysis is one member of this class of strategies. I believe that it is possible to show that none of these strategies is reasonable. However, there are so many of these strategies that the required argument demands something more like a book and less like a short essay. The argument of the following essay is a piece of this larger argument.

Abortion, Induced↗
PubMed1998

Structural characterization and optimization of antibody-selected phage library mimotopes of an antigen associated with autoimmune recurrent thrombosis.

The presence of high titers of anti-cardiolipin antibodies (ACA's) of autoimmune origin, which are known to bind to plasma beta2-glycoprotein I (aka apolipoprotein H), correlates clinically with autoimmune recurrent thrombosis. Soluble beta2-glycoprotein I binds to solid-phase ACA (immobilized on a surface plasmon resonance chip) with a Kd of 1.4 microM, but if the reactants are reversed and beta2-glycoprotein I is on the solid-phase support, then the Kd is 52 nM. This 27-fold difference in affinity reflects the avidity/entropic advantage obtained for an antibody binding to an antigen that is made multivalent because it is attached to a solid phase. A mimotope of this antigen, selected from a phage display peptide library screen with an ACA, has been shown to bind to solid-phase ACA as a phage, using surface plasmon resonance. This peptide is representative of the motif from 37 peptides obtained in a previously reported phage library screen with this ACA (1). A synthetic version of this peptide, referred to as P4, has the sequence: A1G2P3C4I5L6L7A8R9D10R11C12P13G14, and binds to its selecting antibody with a Kd of 42 nM. NMR data indicate that proline-13 is present in both cis and trans configurations, and that these two geometries dramatically affect the overall tertiary structure of the molecule. The peptide lacking this proline binds severalfold better to the ACA, consistent with at least one of these structures having low affinity for binding ACA. Replacement of the arginine-9 position with a proline decreases binding affinity to ACA 10-fold. Another phage library-selected peptide has a proline in position 9, but also has a leucine in position 5, instead of isoleucine. Since its affinity for ACA is nearly as good as that for peptide P4, the phage library screening must have selected for a non-beta-branched amino acid in this position to compensate for the adverse effects of the arginine-9 to proline-9 substitution. The solution structure of a modified version of the antibody-selected phage peptide P4 with the central proline was determined. This peptide has one turn comprised of Ala-Pro-Asp-Arg, with the proline peptide bond in the cis configuration, and another turn that contains the disulfide and adjacent residues. If the disulfide is replaced by a thioether, and the central proline by an alpha-methyl proline, in an attempt to make the peptide more biologically stable, there is little adverse effect on affinity for ACA. The thioether bond/turn is fairly well defined with a Calpha to Calpha separation of 4.9 +/- 0.8 A. The alpha-methyl proline adopts the trans configuration, and this central Ala-(alpha-methyl-Pro)-Asp-Arg turn adopts a distorted type I turn conformation with a probable i to i+3 hydrogen bond. Modeling studies suggest that the proline peptide bond configuration switched from cis to trans in the presence of the alpha-methyl group on proline because of steric hindrance with the beta-carbon of the preceding residue. Overall, this peptidomimetic molecule is structurally very similar to the peptide with natural amino acids, with an rmsd difference of only 1.37 A, when comparing backbone atoms.

Antibodies, Anticardiolipin↗
PubMed1998

A chemically defined, toleragen-based approach for targeting anti-beta2-glycoprotein I antibodies.

Antiphospholipid syndrome is characterized by a prothrombotic state and the presence of beta2-glycoprotein I (beta2-GPI)-dependent antiphospholipid antibodies. The feasibility of a B cell tolerance-based approach for specific reduction of anti-beta2-GPI antibodies was investigated. Anti-beta2-GPI antibodies isolated from a patient with antiphospholipid syndrome were used to screen peptide libraries expressed in phage, resulting in the identification of a phage that specifically bound anti-beta2-GPI antibodies. The phage-displayed peptide was identified and chemically optimized to generate a synthetic 14-mer peptide with an internal thioether linkage (LJP 685) that retained the binding profile of the original phage. LJP 685 was conjugated to a defined, non-immunogenic organic platform to generate a tetravalent presentation of LJP 685 for use as a toleragen. Tetravalent LJP 685 induced a dose-dependent reduction in antibody levels in mice previously immunized and boosted with LJP 685 coupled to the carrier keyhole limpet hemocyanin. These experiments support the technical feasibility of a tolerance-based approach for reducing anti-beta2-GPI antibodies in vivo.

Amino Acid Sequence↗
PubMed1988

Eradication of palpable intradermal murine bladder tumors by systemic interleukin-2 and cyclophosphamide in C3H mice.

The effect of cyclophosphamide on interleukin-2 (IL-2) therapy was investigated using the intradermal MBT-2 tumor in C3H mice. Human recombinant IL-2 (Biogen) was given intraperitoneally at doses ranging from 5,000 to 30,000 U, three times a day for 5 or 11-13 consecutive days beginning on day 10 after tumor implantation. When IL 2 was given alone, mice could not tolerate greater than 5 days of 5,000 U IL 2/injection: Administration of 10,000 and 15,000 U/injection of IL-2 for 5 days resulted in 64% (9 of 14) and 100% (14 of 14) mortality, respectively. Chemotherapeutic agents (cisplatin at 6 mg/kg or JM-8 75 mg/kg) and daily administration of cortisone acetate (75 mg/kg) partially protected mice from IL-2-induced toxic deaths. Coadministration of mannitol showed no protective effect. The combination of IL-2 and CY at 75 or 100 mg/kg, however, dramatically reduced the mortality induced by IL-2 and made it possible to escalate the dose and long-term administration of IL-2. Combination administration of 75 mg/kg CY with 15,000 U/injection of IL-2 for 11-13 days caused tumor regressions and resulted in a 66% (8 of 12) cure rate.

Animals↗
PubMed1987

Plasma levels of beta-endorphin in young and aged human males during the morning hours.

Age-related alterations in plasma levels of beta-endorphin (BE) were investigated in young and aged human males. This was accomplished by obtaining repeated measurements of BE levels in the plasma of young and aged human male subjects during the morning hours, when a diurnal elevation of BE in the plasma is reported to occur. BE was extracted from the plasma and measured by radioimmunoassay. No differences were found in plasma levels of BE between young and elderly males at any time during the time period studied. In addition, the mean level of BE in the plasma during the entire sampling period did not differ between the two age groups. These data suggest that in human males, the levels of BE in the plasma during the morning hours are not modified by aging.

Adolescent↗
PubMed1986

An argument that all prerandomized clinical trials are unethical.

Conversion of slowly accruing conventionally randomized studies to a prerandomized design has apparently been successful in increasing accrual enough so that some of these studies can be completed. Ellenberg (1984) has pointed out some of the ethical dangers of prerandomization. This paper argues that prerandomization must be either unsuccessful or unethical: either conversion to prerandomization will result in no significant increase in the rate of completion of the study or a significant increase in accrual rate will be achieved either at the price of an inadequate attempt to obtain informed consent, at the price of the deceit of patients, or at the price of violations of patient autonomy. The argument of the paper can be sketched as follows: For any given randomized study, either patients prefer one treatment arm to the other or they do not. On the one hand, if they do, then conventional randomization fails. But prerandomization, if done ethically, will fail also. Hence, if prerandomization succeeds in this sort of case, then the trial has been conducted unethically. On the other hand, if patients do not prefer one arm to the other, then prerandomization will succeed. So will conventional randomization. Hence, prerandomization is either unnecessary or unethical. Ellenberg's concerns count as good moral reasons for not prerandomizing if prerandomization is unnecessary. It follows that prerandomization is always wrong.

Clinical Trials as Topic↗
PubMed1985

Release of immunoreactive beta-endorphin in vitro from pituitaries of young and old male rats.

The release of immunoreactive beta-endorphin (IR-BE) in vitro from the anterior pituitary (AP) and the neurointermediate lobe of the pituitary (NIL) from old male rats was significantly greater than from the AP and NIL from young male rats. In addition, the content and concentration of IR-BE in the AP and NIL was significantly greater in old than in young male rats, as was the concentration of IR-BE in the plasma. Chromatographic analysis revealed that in old male rats, the increase in IR-BE contained in and released by the AP and NIL, and found in the plasma, represented an increase in a peptide which coeluted with beta-endorphin rather than beta-lipotropin. These data suggest that both the AP and the NIL contribute to the elevation in plasma levels of IR-BE observed in old male rats, and that the increase in pituitary and plasma IR-BE in old male rats represents an increase in beta-endorphin.

Aging↗
PubMedDate not supplied

Gender and euthanasia.

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Abortion, Legal↗