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Biomedical subjects

E Atkins

Publications and source records attributed to E Atkins.

At least 37 records · Page 2Linked to original sources
PubMed1982

The detection of endotoxin by in vitro production of endogenous pyrogen: comparison with limulus amebocyte lysate gelation.

The sensitivities of leukocyte endogenous pyrogen (EP) production and limulus amebocyte lysate (LAL) gelation to endotoxin from E. coli (minimum i.v. pyrogenic dose 4 ng/kg in rabbits) were determined. Concentrations of 0.5-1.0 ng/ml could be detected by LAL. The minimum endotoxin concentrations which generated detectable EP from 2 X 10(6) monocytes was 10-fold lower (0.05-0.1 ng/ml). At an endotoxin concentration of 0.4 ng/ml the minimum number of monocytes required for detectable EP production was 5 X 10(5). It is concluded that the LAL gelation test cannot safely be used to exclude significant endotoxin contamination in a cellular system where EP production is being measured. The same conclusion applies even more forcibly to the in vitro production of lymphocyte activating factor (LAF, interleukin-1), since it appears that LAF and EP are identical and sub-pyrogenic amounts of EP are easily detectable in the LAF assay.

Animals↗
PubMed1982

The inhibitory effect of polymyxin B on endotoxin-induced endogenous pyrogen production.

The effect of polymyxin B (PMB) on the endogenous pyrogen (EP)-induced property of lipopolysaccharide (LPS) in vitro was examined. PMB inhibited LPS when added to leukocyte suspension 5 min before or up to 30 min after the addition of LPS. The inhibitory effect was dose-related and appeared to be specific for LPS (including naturally occurring endotoxin). EP production in response to a different stimulus (staphylococci) was not prevented even when LPS-PMB complexes were presumably present. These data suggest that when experimental agents are found to stimulate the production of EP or lymphocyte activating factors (LAF, interleukin-1) in vitro, or when apparently spontaneous production of EP or LAF is seen, incubation with PMB may be a useful technique to exclude th effects of endotoxin contamination - especially when negative results have been obtained in the limulus gelation test.

Animals↗
PubMed1981

Longitudinal study of obesity in the National Survey of Health and Development.

In a nationally representative cohort of 5362 children born in one week in March 1946 weights and heights were recorded at 6, 7, 11, 14, 20, and 26 years. Overweight was defined as a weight that exceeded the standard weight for height, age, and sex by more than 20% (relative weight greater than 120%). The prevalence of overweight was 1.7% and 2.9% in boys and girls respectively at 6 years; 2.0% and 3.8% at 7 years; 6.4% and 9.6% at 11 years; 6.5% and 9.6% at 14 years; 5.4% and 6.5% at 20 years; and 12.3% and 11.2% at 26 years. The risk of being overweight in adulthood was related to the degree of overweight in childhood and was about four in 10 for overweight 7-year-olds. Analysis of the data in the reverse direction showed that 7% and 13% respectively of 26-year-old overweight men and women had been overweight at the age of 7. These results suggest that there is no optimal age during childhood for the prediction of overweight in adult life and that excessive weight gain may begin at any time. Overweight children are more likely to remain overweight than their contemporaries of normal weight are to become overweight.

Adolescent↗
PubMed1980

Release of endogenous pyrogen-activating factor from concanavalin A-stimulated human lymphocytes.

Evidence is presented that the mitogen concanavalin A stimulates human lymphocytes to produce a nonpyrogenic lymphokine (LK) that is capable of activating human monocytes but not granulocytes to produce endogenous pyrogen (EP) in vitro. The potency of this preparation should facilitate further studies to purify and characterize this agent and determine its relation to other know LK. It seems likely that this factor, which we have called EP-activating factor (EPAF), plays a significant role in the development of fever in states of delayed hypersensitivity in man.

Concanavalin A↗
PubMed1980

Effect of breast-feeding on plasma cholesterol and weight in young adults.

The relation between breast-feeding and plasma cholesterol level in adult life was examined in a longitudinal study of a sample of people born in 1946. One hundred and seventy-two subjects whose breast-feeding history had been recorded during infancy were examined when they were 32 years old. Women who had been breast-fed had significantly lower mean plasma cholesterol than women who had been bottle-fed (5.4 mmol/l compared with 5.9 mmol/l). For men the difference was smaller and not significant. An unexpected finding was the higher mean weight and skinfold thickness in men who had been breast-fed. These results support the hypothesis that factors acting very early in life affect the risk of disease in adults.

Adult↗
PubMed1980

Release of an endogenous pyrogen from guinea pig leukocytes: the role of T lymphocytes and correlation with suppression (desensitization) of delayed hypersensitivity.

The pathogenesis of fever in delayed hypersensitivity (DH) was studied in guinea pigs immunized with either ovalbumin or bovine gamma-globulin in complete Freund's adjuvant. In vitro incubation of sensitized lymphocytes with the specific antigen used for immunization resulted in the elaboration of a lymphokine-like factor that activated either monocytes or neutrophils to release endogenous pyrogen (EP), the protein that causes fever. Specifically sensitized T cells appeared to be responsible for release of this EP-inducing factor. Desensitization of the dermal DH response to antigen was produced by several large injections of antigen and was associated with a reduced capacity of lymphocytes from such animals to activate phagocytic cells to release EP. This may explain the reduced fever (pyrogenic tolerance) that occurs when repeated injections of antigen are given to sensitized animals. Fever and the dermal response to DH seem to be closely linked reactions that have evolved to defend the host against invading pathogens. In both reactions, phagocytic cells appear to be activated by lymphokines derived from T lymphocytes specifically responding to microbial antigens.

Animals↗
PubMed1979

Fever: pathogenesis, pathophysiology, and purpose.

Fever appears to have evolved in vertebrate hosts as an adaptive mechanism for controlling infection. This phenomenon is produced by certain exogenous (largely microbial) stimuli that activated bone-marrow-derived phagocytes to release a fever-inducing hormone (endogenous pyrogen). Endogenous pyrogen, in turn, circulates to the thermoregulatory center of the brain (preoptic area of the anterior hypothalamus) where it causes an elevation in the "set-point" for normal body temperature. Warm blooded animals produced fever by increasing heat production (through shivering) or reducing heat loss (by peripheral vasoconstriction), whereas cold blooded animals do so only by behavioral mechanisms (seeking a warmer environment). This paper discusses current concepts that involve the mechanism of endogenous pyrogen production, the role of central transmittors, and the probable function of fever in combating disease.

Animals↗
PubMed1979

Clinical fever: its history, manifestations and pathogenesis.

A short summary of some aspects of the history of clinical fever is presented with special reference to its association with inflammation. The role of bacterial endotoxins and endogenous pyrogen (released from inflammatory cells) in the genesis of human fevers is reviewed. Clinical diseases are tabulated within various broad categories and discussed in relation to the frequency with which they are associated with fever and the probable pathogenetic mechanisms involved. Certain unresolved discrepancies are emphasized in the light of our present knowledge.

Bacterial Infections↗
PubMed1978

Pathogenesis of fever in delayed hypersensitivity: factors influencing release of pyrogen-inducing lymphokines.

In continuing studies on the pathogenesis of fever in states of delayed hypersensitivity, we have investigated the conditions for the release of an endogenous pyrogen (EP)-inducing lymphokine from draining-lymph-node lymphocytes of rabbits with delayed hypersensitivity to bovine gamma globulin. Using doses of 4 X 10(7) to 5 X 10(7) blood leukocytes (BL) as a source of EP, we found that ratios of about 5:1 of viable lymphocytes to BL were required to stimulate the BL to produce detectable amounts of EP in vitro. Both irradiated lymphocytes (1,700 R) as well as those from steroid-treated donors retained their ability to activate BL when incubated with antigen, properties consistent with activated "T" lymphocytes. In experiments to determine effects of temperature and duration of incubation on lymphokine release, the maximum EP-releasing activity was found to be present in supernatants of sensitized lymphocytes incubated with antigen for 18 h at 37 degrees C. These studies have confirmed that sensitized lymphocytes release a soluble, pyrogen-inducing lymphokine when incubated with antigen and further demonstrate that tissue macrophages (Kupffer cells) as well as BL can be activated to produce EP in vitro by this agent.

Animals↗
PubMed1978

Pathogenesis of fever in delayed hypersensitivity: role of monocytes.

The present studies were designed to investigate the role of monocytes in the pathogenesis of fever in delayed hypersensitivity. Adherent rabbit blood monocytes (from both normal and sensitized donors) were separated on Ficoll-Hypaque gradients and incubated with antigen (Ag; ovalbumin) and sensitized draining-lymph-node lymphocytes (or their supernatants) from rabbits with delayed hypersensitivity, and release of endogenous pyrogen was assayed. Results indicated that monocytes are activated to produce endogenous pyrogen by Ag and suspensions of draining-lymph-node cells or by an agent (lymphokine) in the supernatants of sensitized lymphocytes preincubated with Ag. The release of lymphokine was Ag specific and was correlated with the skin test reactivity of the donor rabbits to the sensitizing Ag. No evidence was found that Ag-antibody complexes or (in the case of sensitized monocytes) cytophilic antibodies play a role in the activity of this lymphokine which appears to act selectively on monocytes rather than on granulocytes.

Animals↗
PubMed1978

Effects of fever on host defense mechanisms after infection in the lizard Dipsosaurus dorsalis.

Fever has never been proven beneficial in mammals, although it enhances survival in the lizard D. dorsalis infected with Aeromonas hydrophila. We examined the course of the infection and the function of host defence in febrile (41 degrees) and afebrile (35 degrees or 38 degrees) animals using this model. Infected, febrile lizards had sterile blood cultures, and 1-2 logs fewer bacteria in body tissues 6-12 h after infection. Granulocytes appeared early and in large numbers at the site of inoculation in febrile, but not afebrile, animals. We were unable to demonstrate effects of this small range of temperatures on in vitro growth rates of bacteria, on lizard granulocyte chemotactic or phagocytic functions, or upon serum antibody levels. Our results suggest that fever enhances some aspect of the early inflammatory response, leading to increased leucocyte emigration at the local site and containment of the infection.

Aeromonas↗
PubMed1977

The release of an endogenous pyrogen from guinea pig leukocytes in vitro: a new model for investigating the role of lymphocytes in fevers induced by antigen in hosts with delayed hypersensitivity.

Guinea pig periotoneal exudate (PE) cells incubated overnight in vitro with heat-killed Staphylococci released an endogenous pyrogen (EP) that could be assayed by intravenous injection in rabbits. The febrile responses were linearly related to the dosage of EP over an eightfold range. PE cells derived from guinea pigs with delayed hypersensitivity (DH) to bovine gamma globulin (BGG), also released EP when incubated with antigen in vitro. This reaction was specific and did not occur withe PE cells from normal or complete Freund's adjuvant-sensitized guinea pigs. Studies indicated that monos and/or polymorphonuclear leukocytes rather than lymphocytes were the source of EP. However, when incubated with BGG and sufficient dosages of BGG-sensitized lymphocytes, normal PE cells released EP over a 42 h period. These results suggest that antigen stimulates specifically sensitized lymphocytes to release an agent (perhaps a lymphokine) that activates phagocytic cells to release EP. This model offers unique advantages for investigating in vitro the role of the lymphocyte in antigen-induced fever in DH as well as the relationship of this lymphocyte-induced activity to other known biologic activities mediated by antigen stimulated lymphocytes.

Animals↗