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Biomedical subjects

W Parker

Publications and source records attributed to W Parker.

At least 55 records · Page 3Linked to original sources
PubMed1996

Specificity of xenoreactive anti-Gal alpha 1-3Gal IgM for alpha-galactosyl ligands.

The transplantation of organs from lower animals such as pigs into humans is prevented by a severe rejection reaction initiated by complement fixing xenoreactive natural antibodies. Most anti-pig xenoreactive natural antibodies in humans are thought to recognize Gal alpha 1-3Gal beta 1-4GlcNAc and are also thought to recognize, albeit less avidly, Gal alpha 1-6Glc. Gal alpha 1-6Glc has been used as a ligand for purification of 'anti-Gal alpha 1-3Gal antibodies' and as a therapeutic or reagent to prevent the binding of these antibodies to porcine organs or cells. We tested the specificity of anti-Gal alpha 1-3Gal IgM for Gal alpha 1-6Glc and related saccharides. Based on inhibition of binding of xenoreactive anti-Gal alpha 1-3Gal IgM to porcine cells by soluble saccharides, anti-Gal alpha 1-3Gal IgM in a human serum was found to consist of a mixture of antibodies which have a similar affinity for Gal alpha 1-3Gal but varying affinities for Gal alpha 1-6Glc and other structures. Twenty to 40% of the anti-Gal alpha 1-3Gal IgM from the population tested did not recognize Gal alpha 1-6Glc. The binding of anti-Gal alpha 1-3Gal IgM to Gal alpha 1-6Glc varied widely from individual to individual, some samples lacking almost entirely anti-Gal alpha 1-3Gal IgM which bound to Gal alpha 1-6Glc.

Animals↗
PubMed1996

Perfectionism and suicidal preoccupation.

One hundred twenty-nine undergraduate students were assessed for suicidal preoccupation, using the Alabama Adolescent Health Survey (AAHS) and selected cards from the Thematic Apperception Test (TAT). They were also administered the Multidimensional Perfectionism Scale (MPS) to assess perfectionistic tendencies. Objective scoring of the TAT was found to be highly reliable. Canonical correlational analyses were nonsignificant for a relationship between perfectionism and suicidal themes on the TAT. However, the more direct questions of the AAHS relating to suicide were significantly related to perfectionism. Results suggest that passive perfectionists who procrastinate out of fear of making mistakes are more likely to be preoccupied with suicide, unlike perfectionists whose strivings produce achievement. High personal standards and parental expectations do not appear related to suicidal preoccupations.

Adult↗
PubMed1996

Establishment of Demodex canis on canine skin engrafted onto scid-beige mice.

A small animal model of canine demodicosis is described. Normal canine skin was engrafted onto scid (severe combined immunodeficient)-beige mice, which lack functional B and T lymphocytes and have reduced natural killer cell activity. The xenografts were later infected with Demodex canis collected from a dog with demodicosis. At 30-112 days following infection, mites were seen histologically in the canine hair follicles of the engrafted skin. Demodex canis adults, nymphs, larvae, and eggs were present in samples macerated in sodium hydroxide. Mite infestations could not be demonstrated in the mouse skin, nor were mites passed from the infected graft to uninfected skin grafts on in-contact mice. This model may be utilized to assess the efficacy of miticidal treatments, to evaluate the importance of specific components of the immune response, and to study the biology of D. canis.

Animals↗
PubMed1995

The humoral immune response in humans following cross-perfusion of porcine organs.

A major question in xenotransplantation is the nature of the humoral response that would occur following the transplantation of a xenogeneic organ into an immunosuppressed recipient as such a response could mediate delayed types of injury to the graft. To begin to address this issue we characterized the changes in the properties of xenoreactive antibodies occurring in patients exposed to porcine organs under conditions simulating transplantation. In two patients whose blood had been cross-perfused through porcine livers as a treatment for hepatic failure, the titer of xenoreactive IgM increased by four-fold and the titer of xenoreactive IgG increased by sixty-fold within ten days after perfusion procedures. The xenoreactive IgM and IgG antibodies were specific for Gal alpha 1-3Gal based on binding to porcine endothelial cells and bovine thyroglobulin, which express this determinant, and on the decrease in binding following treatment of porcine endothelial cells or bovine thyroglobulin with alpha-galactosidase. The sequential addition to endothelial cells of amounts of serum known to saturate antibody-binding sites obtained before and ten days after perfusion of porcine organs revealed no increase in binding of IgM above the level observed with serum obtained before perfusion, suggesting that new determinants were not identified. Moreover, the functional avidity of binding to porcine endothelial cells of IgM in serum obtained before and ten days after perfusion of porcine organs was unchanged. Even at later times, the presence of newly elicited antibodies against porcine aortic endothelial cell targets was not detected. Thus, exposure to porcine antigens in a vascularized organ results in increases in the levels of xenoreactive IgM and IgG antibodies--however, these antibodies exhibit properties similar to natural antibodies.

Adult↗
PubMed1995

Cardiac xenografts between primate species provide evidence for the importance of the alpha-galactosyl determinant in hyperacute rejection.

Transplants performed between phylogenetically disparate species are subject to hyperacute rejection initiated by binding of xenoreactive natural Abs to endothelium in the donor organ. Binding of these Abs activates complement, leading to tissue injury and destruction of the graft. Human xenoreactive natural Abs recognize Gal alpha 1-3Gal beta 1-4GlcNAc (galactose alpha 1-3galactose beta 1-4-N-acetylglucosame); however, the relative importance of this Ag in graft rejection has not been proved. The present study was conducted to test the potential importance of alpha-galactosyl (alpha-Gal) determinants in the pathogenesis of hyperacute rejection. To this end, hearts (n = 3) from New World monkeys (Saimiri scureus, squirrel monkey), which can synthesize Gal alpha 1-3Gal, were transplanted heterotopically into Old World monkeys (Papio species, baboon), which do not synthesize Gal alpha 1-3Gal determinants and which have circulating anti-alpha Gal Abs. The xenografts were rejected in 51 to 56 min (mean +/- SD = 53.3 +/- 2.5), results similar to those observed in porcine grafts transplanted into baboons. Histologic analysis of the hearts revealed thrombosis and intraparenchymal hemorrhage and immune deposits consisting of IgM, Clq, C3, C4, C5b, and the membrane attack complex, but not properdin or factor B of the recipient deposited on graft endothelium. Sera obtained from baboons after perfusion of squirrel monkey kidneys revealed depletion of alpha-Gal-specific Abs and anti-pig endothelial cell Abs. These findings provide strong evidence that the Abs that accumulate in New World monkey organs during perfusion with baboon blood are the same Abs that would accumulate in a porcine organ transplanted into a primate and suggest that hyperacute rejection is not necessarily a reflection of phylogenetic distance but that the expression of terminal alpha-Gal residues provides an adequate target to initiate that process.

Animals↗
PubMed1995

Menière's disease. Etiologic considerations.

This article explores the evidence for a common vascular pathophysiology for idiopathic Menière's disease and migraine. After retrospectively reviewing 85 cases of Menière's disease, it is concluded that (1) migraine occurs more often in patients with Menière's disease than in the general population, (2) the classic symptoms of Menière's disease can be part of a migraine attack, (3) symptoms of Menière's disease may be associated with a migraine attack without headache (migraine equivalent), (4) treatment for the migraine with methysergide maleate or prednisone may also improve the symptoms of Menière's disease, and (5) prospective studies with adequate follow-up are needed to further investigate this association.

Adult↗
PubMed1995

Purification and characterization of a 60-kDa protein from oat, formerly known as a TCP1-related chaperone.

Recently, Mummert et al. [Nature 363, 644-648 (1993)] isolated a proposed TCP1-related chaperone. Here we report several findings concerning the protein which they sequenced. Two similar N-terminal sequences were obtained from this abundant 60-kDa protein. Internal sequences were also acquired by protease digestion. Initially it was believed the protein was able to completely inhibit citrate synthase aggregation, but later purifications demonstrated that the 60-kDa polypeptide lacked both chaperone activity and the previously reported kinase activity [Grimm et al., Planta 178, 199-206 (1989)]. It is now our belief that this protein is neither a chaperone nor a kinase.

Amino Acid Sequence↗
PubMed1995

Xenoreactive natural antibodies in the world of natural antibodies: typical or unique?

Xenoreactive natural antibodies are thought to be responsible for initiating the hyperacute rejection of porcine organs transplanted into primates. Progress has been made in recent years in the characterization of the specificity and functions of these antibodies. Xenoreactive natural antibodies recognize Gal alpha 1-3Gal, a carbohydrate related to the blood group A and blood group B antigens. The presence of Gal alpha 1-3Gal may not be sufficient to allow the binding of xenoreactive natural antibodies under physiological conditions; rather, the clustering of Gal alpha 1-3Gal determinants may dictate the extent to which xenoreactive natural antibodies attach to surfaces on which Gal alpha 1-3Gal is expressed. The predominant role of xenoreactive natural antibodies in the pathogenesis of hyperacute rejection in porcine-to-primate xenotransplantation involves the activation of complement. Complement activation is mediated by IgM, not IgG xenoreactive natural antibodies. Based on functional avidity, thermal binding optima, thermal liability and homogeneity of binding interactions, xenoreactive natural IgM appear to be members of a family of natural antibodies which includes isohaemagglutinins. The classification of xenoreactive antibodies and isohaemagglutinins into a family of antibodies may provide further insight into the nature and physiological functions of xenoreactive natural antibodies.

Animals↗
PubMed1994

Characterization and affinity isolation of xenoreactive human natural antibodies.

Natural Abs, which are thought to provide an initial defense against invasive microorganisms, include isohemagglutinins, anti-phosphatidylcholine Abs, and anti-alpha-galactose Abs. We have evaluated the physiologic properties of the fraction of human natural Abs that bind to porcine endothelial cells and that would, as a result, initiate the rejection of a porcine organ transplanted into a human. The concentration of xenoreactive IgM in the serum varied widely in the population (5 to 105 micrograms/ml), but was highly dependent on the concentration of IgM in the serum (r = 0.85). Despite this variation and the potential diversity of epitopes recognized, human xenoreactive natural Abs exhibited surprisingly homogeneous binding characteristics, both in one individual and in the population. The apparent avidity determined by using a direct ELISA yielded a functional dissociation constant of 10(-8) M to 10(-10) M, depending on the temperature used. This high functional Kd apparently results from polyvalent interactions between the IgM and the porcine cell surface. Although the xenoreactive IgMs were absorbed by structurally diverse molecules such as ssDNA and thyroglobulin, about 80% of the xenoreactive Abs were specific for the terminal alpha-galactose determinant. A method was developed for affinity isolation of xenoreactive natural Abs by using a thermal extraction procedure. The method quantitatively accounts for all xenoreactive IgM, yielding functional IgM as evidenced by Ag binding and complement activation. Given the overlapping specificity of xenoreactive Abs in the population and the homogeneity of the functional Kd, the natural humoral immunologic barrier to xenotransplantation may be far less formidable than previously thought.

Animals↗
PubMed1992

N-terminal domain of Avena phytochrome: interactions with sodium dodecyl sulfate micelles and N-terminal chain truncated phytochrome.

Phytochrome is the ubiquitous red light photoreceptor present in plants. Properties of the 6-kDa end terminal region of phytochrome A (PHYA from etiolated Avena) have been investigated by the use of synthetic polypeptide fragments corresponding to that region. This region of the phytochrome A protein has been viewed as a possible functional site due to the large differences in the sequence's conformation and exposure between the Pr (red light-absorbing form) and Pfr (far-red light-absorbing, gene-regulating form) species of phytochrome A. Hydrophobic moment calculations reveal amphiphilic helical potential in this section of the protein, consistent with the folding of the N-terminal region onto a hydrophobic chromophore/chromophore pocket. A large N-terminal synthetic peptide also demonstrated helical folding in the presence of SDS micelles. This experimental evidence indicates that the N-terminal alpha-helical folding upon conversion of the regulatorily inactive Pr to the active Pfr form of phytochrome A is likely driven at least in part by amphiphilic helix stabilization. Further, the large synthetic peptide was spectrally demonstrated to interact with phytochrome A lacking the N-terminal region. The formation of this nativelike complex may provide us with a tool for both biophysical and physiological studies on the mechanism of phytochrome A signal transduction.

Edible Grain↗
PubMed1992

Protein structures in SDS micelle-protein complexes.

Sodium dodecyl sulfate (SDS) is used more often than any other detergent as an excellent denaturing or "unfolding" detergent. However, formation of ordered structure (alpha-helix or beta-sheet) in certain peptides is known to be induced by interaction with SDS micelles. The SDS-induced structures formed by these peptides are amphiphilic, having both a hydrophobic and a hydrophilic face. Previous work in this area has revealed that SDS induces helical folding in a wide variety of non-helical proteins. Here, we describe the interaction of several structurally unrelated proteins with SDS micelles and the correlation of these structures to helical amphiphilic regions present in the primary sequence. It is likely that the ability of native nonordered protein structures to form induced amphiphilic ordered structures is rather common.

Animals↗
PubMed1991

Migraine and the vestibular system in adults.

The purpose of this paper is to explore the relationships between migraine and the vestibular system in adults. A review of the literature on migraine reveals that paroxysmal vertigo is not uncommonly associated with migraine in various temporal relationships with headache and/or other neurologic symptoms. Vertigo (or nonvertiginous dizziness) may be the chief presenting complaint sometimes masking less dramatic symptoms causing patients to be directed to an otolaryngologist. Meticulous family, past personal, and present history are necessary to produce the information leading to suspicion of the association of paroxysmal vertigo with the migraine diathesis. A careful prospective study of a large neurotologic population seems indicated to further define this relationship leading to diagnostic and therapeutic benefits. Sixteen cases are presented, six of them in detail.

Humans↗