Search PubMed⌕ Search

Biomedical subjects

J S Sullivan

Publications and source records attributed to J S Sullivan.

87 records · Page 5Linked to original sources

Enteric bacteria and HLA-B27 associated cell surface modification in patients with seronegative spondarthritis.

Cytotoxic studies indicate cross-reactivity between some enteric organisms and cells obtained from the majority of patients with ankylosing spondylitis. Preliminary studies suggest that the factor responsible for cross-reactivity may be generated by a bacterial plasmid. However, the mechanism mediating the interaction between the HLA-B27 positive cell and the bacterial antigen is at present unknown.

Cross Reactions↗

Possible role of enteric organisms in the pathogenesis of ankylosing spondylitis and other seronegative arthropathies.

One-hundred eighty-five clinical isolates of Salmonella sp., Shigella sp., Escherichia coli, and Campylobacter sp. were tested for their ability to absorb the lymphocytotoxic activity of an antiserum (anti-Klebsiella sp. K43) directed against a specific HLA-B27-associated cell surface determinant on the lymphocytes of patients with ankylosing spondylitis (AS). Seven of these isolates (three Salmonella sp., two Shigella sp., one E. coli, and one Campylobacter sp.) were found to cross-react with the B27-positive cells of AS patients (B27+ AS+); an E. coli organism isolated from the rectal swab of an HLA-B27-negative clinically normal individual also cross-reacted with B27+ AS+ cells. These cross-reactive enteric organisms elaborate a factor (modifying factor) which specifically modifies the B27-positive lymphocytes of normal individuals; this factor is structurally and antigenically related to a functionally similar factor secreted by certain isolates of Klebsiella sp. These data suggest that certain enteric organisms share a common determinant which cross-reacts with B27+ AS+ cells. It is suggested that this cross-reactivity is somehow related to an early event in the pathogenesis of AS and possibly of other seronegative arthropathies.

Chromatography, Gel↗

A factor shed by lymphoblastoid cell lines of HLA-B27 positive patients with ankylosing spondylitis, specifically modifies the cells of HLA-B27 positive normal individuals.

Epstein-Barr virus transformed lymphoblastoid cell lines from HLA-B27 positive individuals with ankylosing spondylitis (B27+AS+) release, into the culture medium, a factor capable of specifically modifying the HLA-B27 positive lymphocytes of normal individuals (B27+AS-); this modification results in a phenotypic change similar to that seen on B27+AS+ lymphocytes. This lymphoblastoid cell line derived factor appears to be physically and functionally similar to a factor present in the culture filtrate of certain Klebsiella isolates. Biogel P-100 chromatography of the material released from the cell line indicated a mol.wt of 25,000-30,000, similar to that of the Klebsiella derived factor. Chromatofocusing on a PBE 94 column revealed that cell line derived factor had an isoelectric point of 5.5 (cf. pI 5.4 for the Klebsiella derived factor). Immunoadsorption experiments suggest that the factor from the B27+AS+ cell line shares antigenic determinants with a cell surface component present on certain Klebsiella isolates. These results will form the basis for future studies on the nature of the interaction between HLA-B27 and certain enteric organisms and their products. A better understanding of this association should elucidate some of the early events in the pathogenesis of the seronegative arthropathies.

Cell Line↗

The isolation and chemical characterization of skeletal muscle microsomes from swine susceptible to malignant hyperpyrexia.

1. The anaesthetic complication malignant hyperpyrexia (MH) occurs in individuals and swine with a muscle membrane abnormality. 2. In an attempt to characterize this abnormality, the lipid and protein composition of muscle membranes from MH-susceptible swine was examined and compared with controls. 3. No significant abnormality in the membrane protein or lipid content of MH-susceptible muscle was detected.

Animals↗

Temperature dependence of muscle function in malignant hyperpyrexia-susceptible swine.

Contractures induced by halothane, caffeine, suxamethonium chloride and potassium in malignant hyperpyrexia-susceptible (MHS) and control swine skeletal muscle preparations were temperature-dependent, but differed in their temperature response profiles. Increasing the temperatures from 20 degrees C to 37 degrees C increased drug-induced contractures in MHS muscle. At 5 degrees C drug-induced contractures were not inhibited by dantrolene sodium, deuterium oxide or glycerination in either MHS or control muscle. These observations give further support to the view that the abnormality in MHS skeletal muscle is associated with the mechanism of excitation-contraction coupling.

Animals↗

The effect of the calcium ion antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate on malignant hyperpyrexia-susceptible porcine skeletal muscle.

In malignant hyperpyrexia susceptible (MHS) porcine skeletal muscle, a low concentration (100 mumol/l) of the calcium ion antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) inhibited KCl-induced contractures, but potentiated contractures induced by halothane, caffeine and succinylcholine. Higher concentrations of TMB-8 (333 mumol/l to 1 mmol/l) contracted MHS muscle, but had little effect on muscle tension in control preparations. Treatments which inhibit excitation-contraction coupling abolished TMB-8-induced hyper-reactivity in MHS muscle. TMB-8 (50 mumol/l and 1 mmol/l) did not alter 45Ca2+ levels in actively loaded microsomal preparations from MHS swine. These results suggest that in malignant hyperpyrexia the primary abnormality occurs proximal to the release of calcium from the sarcoplasmic reticulum, probably at the level of excitation-contraction coupling.

Animals↗

Plasmodium coatneyi: observations on periodicity, mosquito infection, and transmission to Macaca mulatta monkeys.

Plasmodium coatneyi has adapted well to experimental studies with Macaca mulatta monkeys and Anopheles dirus mosquitoes. Studies were made to determine 1) the course of asexual parasitemia, 2) periods when infective gametocytes were produced, 3) the laboratory-reared mosquitoes susceptible to infection, 4) the mosquito most capable of transmitting the infection to monkeys via bite, 5) the pattern of recrudescence, and 6) the prepatent periods following the bites of infected An. dirus mosquitoes. The period when infective gametocytes are produced is concentrated primarily in the first week when parasitemia exceeds 1,000/microl. Mosquitoes were more heavily infected on days when the asexual parasite counts were highest. Gametocyte counts were generally low. Mature forms of the parasite markedly sequestered giving a pattern of high-low periodicity. Anopheles dirus and An. freeborni mosquitoes were nearly equal in terms of their ability to support oocyst development. Other species (An. stephensi, An. maculatus, and An. gambiae.) were less supportive. High sporozoite densities in the salivary glands were frequently produced in An. dirus and sporozoite transmission was obtained via the bites of these mosquitoes after 12-18 days of extrinsic incubation. Prepatent periods ranged from 10 to 15 days. The presence of frequent parasitic recrudescences suggests mechanisms similar to that seen in human infections with P. falciparum. It is proposed that P. coatneyi in M. mulatta monkeys can be a suitable model for studies on cerebral pathology, vaccine efficacy, and the testing of antimalarial drugs.

Animals↗