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Biomedical subjects

J S Sullivan

Publications and source records attributed to J S Sullivan.

At least 73 records · Page 4Linked to original sources

Correlation of plasma cytokine elevations with mortality rate in children with sepsis.

Cytokines are thought to be important endogenous mediators of the host immune response to bacterial infection. We hypothesized that plasma levels of cytokines are elevated in children with sepsis and that the magnitude of elevation of these cytokines is correlated with severity of illness and mortality rate. We determined plasma levels of tumor necrosis factor, interleukin-6, and interleukin-1 in 21 children with sepsis. Plasma samples were collected at presentation and at 12, 24, and 48 hours thereafter. Cytokine levels were elevated in pediatric patients with bacterial sepsis during the first 48 hours after presentation; levels were undetectable in study control subjects. The tumor necrosis factor and interleukin-6 levels (p less than 0.001), as well as levels of interleukin-1 (p = 0.05), were significantly higher in nonsurvivors than in survivors and were independent of severity of illness (pediatric risk of mortality (PRISM) score) at presentation. Elevations of tumor necrosis factor and interleukin-6 were sustained for longer than 24 to 48 hours in nonsurvivors: II-1 concentrations were significantly increased only at time zero. Of 11 children with an interleukin-6 value greater than 2 ng/ml during the first 48 hours, 10 died; only one of 10 not reaching that level died (p less than 0.001). Cytokines were elevated as frequently with gram-positive as with gram-negative infections. We speculate that cytokine determinations may identify children who might benefit from immunotherapeutic interventions.

Adolescent↗

A role for tumour necrosis factor-alpha in the human mixed lymphocyte culture reaction.

The possible role and influence of tumour necrosis factor-alpha (TNF-alpha) in the human mixed lymphocyte culture (MLC) reaction was investigated. Polyclonal rabbit sera to recombinant human-TNF-alpha (rhTNF-alpha) consistently inhibited the MLC, and this could be reversed by simultaneous addition of rhTNF-alpha to the culture medium. Under optimal cell culture conditions, the exogenous addition of 1000 U/mL of rh TNF-alpha had a variable but generally small enhancing effect on the MLC reaction. Additional studies have clearly highlighted the importance of MLC assay conditions in influencing the effect of exogenous rhTNF-alpha. Enhancement of the MLC reaction was only consistently observed under suboptimal cell culture conditions. While the present study clearly supports an important role for TNF in controlling the proliferative response in the human MLC reaction it also highlights the influence of in vitro tissue culture conditions in determining the effect of exogenous TNF-alpha in this assay.

Humans↗

Effect of methylene blue on estrogen-receptor activity.

Methylene blue in a 1% sterile solution for injection to help localize occult breast tumor was shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with methylene blue. Cytosols treated with 0.1% methylene blue, a clinically significant level, demonstrated a substantially lower ERP binding capacity compared with control cytosols. This alteration was found to be due to a reduction in specific binding capacity and not to an alteration in apparent cytosol protein concentration. The use of methylene blue for occult breast tumor localization is not recommended when an ERP binding-capacity assay is anticipated.

Biopsy, Needle↗

Noninterference of isosulfan blue on estrogen-receptor activity.

Because a 1% sterile solution of methylene blue used for occult breast tumor localization has been shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay, isosulfan blue in a 1% injection was studied as a potential alternate stain. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with isosulfan blue. No modification of the ERP-specific binding capacity was found with this stain. The use of isosulfan blue for localization of occult breast tumor is suggested when an ERP binding capacity assay is anticipated.

Biopsy, Needle↗

Nutritional value of quality protein maize and food corn for starter and growth pigs.

Growth traits with starter and grower pigs and a digestion trial were conducted to compare the nutritional value of Quality Protein Maize (QPM), food corn and conventional feed corn. The QPM, food and feed corn contained .45, .31 and .29% lysine, respectively. The growth trials evaluated a QPM-soybean meal diet formulated on a lysine basis (.96% in starter and .7% in grower diets) and four diets arranged in a 2 (food corn vs feed corn) X 2 (low vs high soybean meal) factorial. Soybean meal was either added in the same amount as in the QPM diet or was added to provide the lysine content of the QPM diet. Performance was similar for pigs fed food corn and feed corn in both trials. The QPM diets resulted in greater performance than food and feed corn diets containing the same level of soybean meal supplementation; starter pigs were more (P less than .10) efficient and grower pigs had a higher (P less than .01) rate and efficiency of gain. However, performance of pigs fed the QPM diets was not equal to that of pigs fed isolysinic food and feed corn diets; growth rate was lower (P less than .05) in starter pigs and gain:feed was lower (P less than .05) in grower pigs. Diets in the digestion trial consisted of the corns plus 3.25% casein. Energy digestibility was similar for all diets. Ileal N and amino acid digestibilities were highest for QPM, intermediate for food corn and lowest for feed corn. In most instances, these differences were significant (P less than .05). Apparent biological value was highest (P less than .05) for QPM. These trials indicate that food corn and feed corn have similar nutritional value, and that starter and grower pigs can benefit from the higher protein quality of QPM.

Animal Feed↗

Cross-reacting bacterial determinants in ankylosing spondylitis.

The importance of the association between the human histocompatibility antigen human leukocyte antigen-B27 and ankylosing spondylitis is undisputed, but its biologic significance remains unresolved. We have demonstrated specific cross reactivity between a range of enteric bacteria and a specific determinant found only on the surfaces of cells from human leukocyte antigen-B27-positive persons with ankylosing spondylitis. We have proposed that the genetic element coding for this cross-reactive determinant is mobile and that its acquisition by B27-positive cells in vivo represents an important step in the eventual development of ankylosing spondylitis.

Antigens, Bacterial↗

An antiserum to a disease-associated factor from the cells of an HLA-B27 positive patient with ankylosing spondylitis specifically recognizes an HLA-B27 associated determinant.

Antiserum raised to a factor elaborated by a lymphoblastoid cell line derived from the peripheral blood cells of an HLA-B27 positive patient with ankylosing spondylitis specifically lyses the B27 positive, but not the B27 negative, cells of ankylosing spondylitis patients. The cells of B27 positive and B27 negative normal controls are not lysed. This serum has similar specificity to antisera against cross-reactive bacteria.

Cell Line↗

Cytotoxic T lymphocytes against disease-associated determinant(s) in ankylosing spondylitis.

Cytotoxic T lymphocytes, induced by stimulating the PBMC of an HLA-B27+ normal individual (B27+, AS-) with the PBMC of an HLA-identical sibling suffering from ankylosing spondylitis (AS) (B27+, AS+), specifically lyse B27+, AS+ PBMC but not PBMC from HLA-27+ or B27-, AS- normal controls, or from HLA-B27- AS patients (B27-,AS+). CTL of similar specificity can also be raised by immunizing in vitro B27+,AS- cells with autologous cells modified by cross-reactive bacterial antigens. These results suggest that CTL can recognize certain bacterial antigens in association with HLA-B27 and that this interaction may lead to an inflammatory episode during the initial stages of the disease.

Escherichia coli↗

Biochemical studies on a factor isolated from Klebsiella K43-BTS1 that cross-reacts with cells from HLA-B27 positive patients with ankylosing spondylitis.

A component of the cell walls of certain enteric bacteria has been identified that cross-reacts with an HLA-B27-associated cell-surface structure on lymphocytes and other cell types from patients with ankylosing spondylitis. This component, or "modifying factor," from one particular organism, Klebsiella K43-BTS1, has been studied in detail. A purification scheme has been developed using preparative electrofocusing and gel-permeation high performance liquid chromatography techniques and the purified material used in various characterization studies. A previous study demonstrated that the modifying factor has an approximate molecular weight of 30,000 and an isoelectric point of 5.4-5.5. In this study two-dimensional gel electrophoresis experiments demonstrated that the modifying factor is associated with a single protein component of the cell wall of this organism. Pronase and papain destroyed the modifying factor activity whereas trypsin and alpha-chymotrypsin degraded the factor into smaller fragments without destroying its ability to modify B27+ AS- lymphocytes. Neuraminidase did not affect the modifying factor itself but did affect B27+ AS- lymphocytes such that they became unresponsive to modification. Sugar inhibition studies suggested that sugar groups are probably not involved in the function of the modifying factor. The availability of purified modifying factor should permit more detailed chemical analyses as well as functional studies to determine the significance of this molecule to the pathogenesis of ankylosing spondylitis.

Antibody-Dependent Cell Cytotoxicity↗

The modification of HLA-B27-positive lymphocytes by the culture filtrate of Klebsiella K43 BTS 1 is a metabolically active process.

The culture filtrate of some bacteria contains a modifying factor which specifically interacts with the cells of HLA-B27-positive normal individuals (BS+ AS-); this modification results in a serologically detectable change similar to that seen on the cells of patients with ankylosing spondylitis (B27+ AS+). Puromycin, 5-azacytidine, actinomycin D, cyclosporin A, dexamethasone, indomethacin, colchicine, quinacrine, chlorpromazine but not tunicamycin can effectively inhibit the in vitro modification of HLA-B27-positive lymphocytes from normal individuals. These studies suggest that a number of different metabolic pathways may be involved in the modification of B27+ AS- lymphocytes by certain enteric antigens.

Antigens, Bacterial↗